Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(1aR,2Z,4E,6Z,14R)-8-chloro-9,11-dihydroxy-14-methyl-6-[[(piperidin-1-ylacetyl)oxy]imino]-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-6-([[(dimethylamino)acetyl]oxy]imino)-9,11-dihydroxy-14-methyl-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-14-methyl-6-(methylimino)-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-14-methyl-6-[[(piperidin-1-ylcarbonyl)oxy]imino]-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-6-(hydroxyimino)-14-methyl-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
(1aS,2Z,15R,16aR)-9-chloro-10,12-dihydroxy-15-methyl-1a,15,16,16a-tetrahydro-1H-7,4-(metheno)cyclopropa[h][12,2,3,4]benzoxatriazacyclopentadecin-13(8H)-one
-
-
(1R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethyl-2,3-dihydro-1H-isoindole-1-carboxamide
-
-
(3R,5E,9E,11Z)-13-chloro-7,14,16-trihydroxy-3-methyl-11-[[(piperidin-1-ylacetyl)oxy]imino]-3,4,7,8,11,12-hexahydro-1H-2-benzoxacyclotetradecin-1-one
-
-
(3S)-14,16-dihydroxy-3-methyl-3,4,5,6,9,10,11,12-octahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-amino-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
-
IPI-493
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[(4-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]benzoyl)amino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[(4-[[benzyl(ethyl)amino]methyl]benzoyl)amino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-20-chloro-13,19-dihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
-
-
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-(carbamoyloxy)-13,20,22-trihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3-oxo-N-(prop-2-en-1-yl)-2-azabicyclo[16.3.1]docosa-1(22),4,6,10,18,20-hexaen-19-aminium chloride
(4E,6Z,8S,9S,10E,12S,13R,14S,16S,17R)-22-hydroxy-8,13,14,17-tetramethoxy-4,10,12,16,20-pentamethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
-
-
(4E,8S,9S,10E,12S,13R,14S,16R)-13,20-dihydroxy-8,14-dimethoxy-10,12,16-trimethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(22),4,10,18,20-pentaen-9-yl carbamate
(5-[4-amino-6-[(2-methoxyphenyl)sulfanyl]-1,3,5-triazin-2-yl]-2,4-dichlorophenoxy)acetonitrile
-
-
(5E)-5-[(1-benzyl-1H-indol-3-yl)methylidene]-1-(2-fluorocyclohexyl)pyrimidine-2,4,6(1H,3H,5H)-trione
-
-
(5E,9E,11Z)-13-chloro-14,16-dihydroxy-11-[[(piperidin-1-ylacetyl)oxy]imino]-3,4,7,8,11,12-hexahydro-1H-2-benzoxacyclotetradecin-1-one
-
-
(5Z)-7-[4-fluoro-2-(pyridin-3-yl)phenyl]-5-(hydroxyimino)-4-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine
-
-
(7R)-2-amino-7-[5-(6-methoxypyrazin-2-yl)-1,3-thiazol-4-yl]-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one
-
-
1,3-dihydro-2H-isoindol-2-yl[2,4-dihydroxy-5-(propan-2-yl)phenyl]methanone
-
-
1,3-dihydro-2H-isoindol-2-yl[6-hydroxy-3-(3-methylbenzyl)-1H-indazol-5-yl]methanone
-
-
1-(3H-imidazo[4,5-c]pyridin-2-yl)-2,3-dihydro-5H-pyrrolo[2,1-a]isoindol-5-one
-
-
1-(4-aminoquinazolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indol-4-one
-
-
1-(5-ethyl-2,4-dihydroxyphenyl)-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one
-
-
1-(6-amino-9H-purin-8-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one
-
-
1-[4-(2-[6-amino-8-[(7-bromo-2,3-dihydro-1,4-benzodioxin-6-yl)sulfanyl]-3H-purin-3-yl]ethyl)piperidin-1-yl]-2-hydroxy-2-methylpropan-1-one
-
-
17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin
17-(allylamino)-17-demethoxygeldanamycin
-
-
17-allyl-amino-17-demethoxygeldanamycin
-
0.002 mM, 20% inhibition
17-allylamino-17-demethoxygeldanamycin
i.e. tanespimycin, binding kinetics, overview
17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride
-
-
17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride
-
-
2'-methoxy-5-[4-(2-methoxyethyl)-4H-1,2,4-triazol-3-yl]-5'-(propan-2-yl)biphenyl-2,4-diol
-
-
2,4-dihydroxy-5-[5-hydroxy-4-(2-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-methyl-N-pentylbenzamide
-
-
2,4-dihydroxy-5-[5-hydroxy-4-(2-methylphenyl)-4H-1,2,4-triazol-3-yl]-N-methyl-N-[2-(3-methylphenyl)ethyl]benzamide
-
-
2,4-dihydroxy-N-methyl-N-(3-methylbenzyl)-5-[1-(2-methylphenyl)-1H-pyrazol-5-yl]benzamide
-
-
2,5-dichloro-N-[4-hydroxy-3-(2-hydroxynaphthalen-1-yl)phenyl]benzenesulfonamide
2-(5-[3-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-5-hydroxy-4H-1,2,4-triazol-4-yl]-1H-indol-1-yl)ethyl dihydrogen phosphate
-
-
2-([3-[2-(dimethylamino)ethoxy]-4-methoxyphenyl]amino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide
-
-
2-amino-4-chloro-8-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-5-propyl-7,8-dihydropteridin-6(5H)-one
-
-
2-amino-4-methyl-7-[2-(phenylamino)phenyl]-7,8-dihydroquinazolin-5(6H)-one
-
-
2-amino-4-[2,4-dichloro-5-[3-(pyrrolidin-1-yl)propoxy]phenyl]-N-ethylthieno[2,3-d]pyrimidine-6-carboxamide
-
NVP-BEP800/VER-82576
2-amino-6-benzyl-4-(2,4-dichlorophenyl)-5,6-dihydro-7H-pyrrolo[3,4-d]pyrimidin-7-one
-
-
2-amino-6-chloro-9-[(4-iodo-3,5-dimethylpyridin-2-yl)methyl]-7-[2-(1H-pyrrol-1-yl)ethyl]-7,9-dihydro-8H-purin-8-one
-
-
2-amino-N-ethyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide
-
SNX-7081, weak inhibitor
2-bromo-4-(5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)benzonitrile
-
-
2-chloro-6-(2,4-dichlorophenyl)-9H-purine
-
-
2-chloro-N-[3-(5-ethyl-2,4-dihydroxyphenyl)-1H-pyrazol-4-yl]benzamide
-
-
2-fluoro-6-(tetrahydro-2H-pyran-4-ylamino)-4-(2,3,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamide
-
-
2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]-9-[3-(propan-2-ylamino)propyl]-9H-purin-6-amine
2-[(2-methoxyethyl)amino]-4-(4-oxo-1,2,3,4-tetrahydro-9H-carbazol-9-yl)benzamide
-
-
2-[(6-bromo-1,3-benzodioxol-5-yl)methyl]-1-methyl-5-(propanoylamino)-1H-imidazole-4-carboxamide
-
-
2-[(E)-2-(2-hydroxy-3-methoxyphenyl)ethenyl]-3-(4-methoxycyclohexyl)quinazolin-4(3H)-one
-
-
2-[(E)-2-(2-hydroxy-3-methoxyphenyl)ethenyl]-3-(4-methoxyphenyl)quinazolin-4(3H)-one
2-[2-[(4-methoxy-3,5-dimethyl-3,4-dihydropyridin-2-yl)methyl]-7,8-dihydro-2H-6-thia-1,2,3,5-tetraazaacenaphthylen-7-yl]-N-(5-methyl-1,3-thiazol-2-yl)acetamide
-
-
2-[4-(1-methyl-1H-indol-5-yl)-5-sulfanyl-4H-1,2,4-triazol-3-yl]-6-(propan-2-yl)pyridine-3,5-diol
-
-
2-[6-amino-2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]-9H-purin-9-yl]ethyl sulfamate
-
-
2-[6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl]-N-hydroxyacetamide
-
-
2-[[4-(2-chloro-5-hydroxy-4-methoxyphenyl)-5-cyano-7H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]-N,N-dimethylacetamide
-
-
2-[[5-(1,3-benzodioxol-5-yl)-4-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl]-1-phenylethanone
-
-
2-[[6-(dimethylamino)-1,3-benzodioxol-5-yl]sulfanyl]-1-[2-[(2,2-dimethylpropyl)amino]ethyl]-1H-imidazo[4,5-c]pyridin-4-amine
-
CUDC-305
3,6-diamino-5-cyano-4-(4-methoxy-3-[[3-(trifluoromethyl)benzoyl]amino]phenyl)thieno[2,3-b]pyridine-2-carboxamide
-
-
3-(5-chloro-2,4-dihydroxyphenyl)-N-(4-fluorophenyl)-4H-pyrazole-4-carboxamide
-
-
3-(5-chloro-2,4-dihydroxyphenyl)-N-(4-methoxyphenyl)-4H-pyrazole-4-carboxamide
-
-
3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide
3-(5-chloro-2,4-dihydroxyphenyl)-N-[3-(trifluoromethyl)phenyl]-4H-pyrazole-4-carboxamide
-
-
3-(cyclopentylmethyl)-6-hydroxy-N-methyl-N-[4-(morpholin-4-yl)phenyl]-1H-indazole-5-carboxamide
-
-
3-benzyl-4-fluoro-1H-indazol-6-ol
-
-
3-[(4-hydroxycyclohexyl)amino]-2',3'-dimethoxybiphenyl-4-carbonitrile
-
-
3-[(E)-[2-[(2-amino-6-methylpyrimidin-4-yl)ethynyl]benzylidene]amino]-1,3-oxazolidin-2-one
4-(1,3-benzodioxol-5-yl)-3-(5-ethyl-2,4-dihydroxyphenyl)-1H-pyrazole-5-carboxylic acid
4-(1-phenyl-1H-1,2,3-triazol-4-yl)-6-(propan-2-yl)benzene-1,3-diol
-
-
4-(2,4-dichloro-5-methoxyphenyl)-2,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
-
4-(2,4-dichloro-5-methoxyphenyl)-2-[2-(diethylamino)ethoxy]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
-
-
4-(2,4-dichlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile
-
-
4-(4-[4-methoxy-3-[methyl(2-methylpropyl)amino]phenyl]-5-sulfanyl-4H-1,2,4-triazol-3-yl)-6-(propan-2-yl)benzene-1,3-diol
-
-
4-(but-2-yn-1-yl)-6-[4-(4-methoxyphenyl)-5-methyl-1,2-oxazol-3-yl]benzene-1,3-diol
-
-
4-([2-carbamoyl-5-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-3a,4,5,6,7,7a-hexahydro-1H-indazol-1-yl]phenyl]amino)cyclohexyl glycinate
-
SNX-5422
4-([2-[3,5-bis(trifluoromethyl)phenyl]-4,5-bis(4-methoxyphenyl)-1H-imidazol-1-yl]methyl)benzoic acid
-
inhibits the ATPase activity of Hsc70 by binding to its ATPase domain
4-amino-11,18,20-trimethyl-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.12,6]docosa-1(21),2(22),3,5,17,19-hexaene-10,16-dione
-
-
4-chloro-6-(2,4-dichlorophenyl)pyrimidin-2-amine
-
-
4-chloro-6-(4-[4-[4-(methylsulfonyl)benzyl]piperazin-1-yl]-1H-pyrazol-3-yl)benzene-1,3-diol
4-chloro-6-(5-[[2-(morpholin-4-yl)ethyl]amino]-1,2-benzoxazol-3-yl)benzene-1,3-diol
4-chloro-6-phenylpyrimidin-2-amine
-
-
4-chloro-6-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
4-chloro-6-[5-(4-ethoxyphenyl)-1,2,3-thiadiazol-4-yl]benzene-1,3-diol
-
-
4-ethyl-6-[4-(1H-imidazol-4-yl)-1H-pyrazol-3-yl]benzene-1,3-diol
4-ethyl-6-[4-(4-methoxynaphthalen-1-yl)-5-sulfanyl-4H-1,2,4-triazol-3-yl]benzene-1,3-diol
-
-
4-ethyl-6-[5-hydroxy-4-(naphthalen-1-yl)-1H-pyrazol-3-yl]benzene-1,3-diol
-
-
4-[2-amino-4-chloro-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]but-3-yn-1-ol
-
-
4-[4-(1,3-benzodioxol-5-yl)-5-methyl-1H-pyrazol-3-yl]-6-ethylbenzene-1,3-diol
-
-
4-[4-(1-methyl-1H-indol-5-yl)-5-[(pyridin-3-ylmethyl)sulfanyl]-4H-1,2,4-triazol-3-yl]-6-(propan-2-yl)benzene-1,3-diol
-
-
4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-methyl-1H-pyrazol-3-yl]-6-ethylbenzene-1,3-diol
4-[4-(2-fluorophenyl)-5-hydroxy-4H-1,2,4-triazol-3-yl]-6-(2-phenylethyl)benzene-1,3-diol
-
-
4-[4-(2-methyl-1,3-thiazol-4-yl)-5-(trifluoromethyl)-1,2-oxazol-3-yl]benzene-1,3-diol
4-[4-(4-benzylpiperazin-1-yl)-1H-pyrazol-3-yl]-6-chlorobenzene-1,3-diol
4-[4-(6-fluoro-1H-benzimidazol-2-yl)-9H-carbazol-9-yl]-2-[(trans-4-hydroxycyclohexyl)amino]benzamide
-
-
4-[4-(diethylamino)phenyl]-5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-1,2-oxazole-3-carboxamide
4-[5-hydroxy-4-(1-methyl-1H-indol-5-yl)-4H-1,2,4-triazol-3-yl]-6-(propan-2-yl)benzene-1,3-diol
-
-
4-[5-hydroxy-4-[4-(morpholin-4-yl)phenyl]-4H-1,2,4-triazol-3-yl]-6-(propan-2-yl)benzene-1,3-diol
-
-
4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-3a,4,5,6,7,7a-hexahydro-1H-indazol-1-yl]-2-[(4-hydroxycyclohexyl)amino]benzamide
-
SNX-2112
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
5-(5-ethyl-2,4-dihydroxyphenyl)-1-(naphthalen-1-yl)-1,3-dihydro-2H-imidazol-2-one
-
-
5-amino-1-(5-aminopentyl)-2-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-1H-imidazole-4-carboxamide
-
-
5-amino-1-[(2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-imidazole-4-carboxamide
-
-
5-hydroxy-4-[5-hydroxy-4-[6-(morpholin-4-yl)pyridin-3-yl]-4H-1,2,4-triazol-3-yl]-2-(propan-2-yl)phenyl dihydrogen phosphate
-
-
5-[1-[(6-[5-[(benzyloxy)carbonyl]-4-biphenyl-4-yl-6-methyl-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]hexanoyl)(hexyl)amino]-2-[(1E)-butylideneamino]-2-oxoethyl]-2-(carboxymethoxy)benzoic acid
-
-
5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-4-[4-(morpholin-4-yl)phenyl]-1,2-oxazole-3-carboxamide
6-(4-benzylpiperazin-1-yl)-2-chloro-9H-purine
-
-
6-bromo-N-[4-(quinolin-3-yl)-9H-fluoren-9-yl]-1,8a-dihydropyrido[2,3-d]pyrimidine-5-carboxamide
-
-
6-chloro-9-[(3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine
-
-
6-chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine
6-chloro-9-[(5-methoxy-4,6-dimethylpyridin-3-yl)methyl]-9H-purin-2-amine
6-[(2R)-2-[(5-fluoro-2-methoxyphenoxy)methyl]pyrrolidin-1-yl]-9H-purine
-
-
6-[5-[(benzyloxy)carbonyl]-4-(4-cyclohexylphenyl)-6-methyl-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]hexanoic acid
-
IC50 value about 0.12-0.2 mM
6-[5-[(benzyloxy)carbonyl]-4-biphenyl-4-yl-6-methyl-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]hexanoic acid
-
IC50 value about 0.12-0.2 mM
7-[2,4-dichloro-6-[2-(1H-pyrazol-1-yl)ethoxy]phenyl][1,3]thiazolo[5,4-d]pyrimidin-5-amine
-
-
8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-(pent-4-yn-1-yl)-9H-purin-6-amine
8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9-(pent-4-yn-1-yl)-9H-purin-6-amine
8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-(pent-4-yn-1-yl)-9H-purin-6-amine
8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]-9H-purin-6-amine
8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9-[2-(cyclopropylamino)ethyl]-9H-purin-6-amine
8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9-[2-[(2,2-dimethylpropyl)amino]ethyl]-9H-purin-6-amine
8-[[5-(diethylamino)pentyl]amino]quinolin-6-ol
-
-
9-butyl-8-(3,4,5-trimethoxybenzyl)-9H-purin-6-amine
9-butyl-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9H-purin-6-amine
9-[2-(tert-butylamino)ethyl]-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine
9-[2-[(2,2-dimethylpropyl)amino]ethyl]-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine
-
-
9-[3-(tert-butylamino)propyl]-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine
Apg2
-
at high concentration (0.002 mM), Agp2 inhibits the ATPase activity of the enzyme
-
apoptozole
-
inhibits Hsc70 activity by binding to its ATPase domain
ATI3387
competitive inhibitor
cyclohexyl 5-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl]-L-norvalinate
-
-
deguelin
-
inhibits HSP90 by interacting with its ATP-binding pocket
diethyl (2-[6-amino-8-[(7-bromo[1,3]thiazolo[4,5-c]pyridin-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
diethyl (2-[6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
diethyl (2-[6-amino-8-[(7-chloro[1,3]thiazolo[4,5-c]pyridin-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
ethyl (4-[3-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-5-sulfanyl-4H-1,2,4-triazol-4-yl]benzyl)carbamate
-
-
ethyl 2-amino-4-(4-bromo-2-chloro-5-methoxyphenyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxylate
-
-
ethyl 4-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-6-methyl-2-oxo-1,2-dihydropyrimidine-5-carboxylate
-
-
Guanidinium chloride
-
approx. 50% uncompetitive inhibition above 0.5 mM
MDC-3100
competitive inhibitor
methyl (2E)-3-[2-amino-4-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)quinazolin-6-yl]prop-2-enoate
-
-
methyl 4-(naphthalen-2-yl)-2-oxo-6-(phenoxymethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
-
IC50 value about 0.12 -0.2 mM
Mg2+
-
above 20 mM, approx. 50% inhibition at 100 mM
N-(4-acetylphenyl)-3-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazole-4-carboxamide
N-(4-acetylphenyl)-3-(5-chloro-2,4-dihydroxyphenyl)-4H-pyrazole-4-carboxamide
-
-
N-benzyl-6-(3-[[(2,6-dichloro-9H-purin-9-yl)acetyl]amino]-8-azabicyclo[3.2.1]oct-8-yl)pyridine-3-carboxamide
-
-
N-butyl-2,4-dihydroxy-5-[(5-hydroxy-1,3-dihydro-2H-isoindol-2-yl)carbonyl]benzamide
-
-
N-ethylmaleimide
-
5 mM, approx. 85% inhibition
N-[2-(dimethylamino)ethyl]-6-[3-[(4-methoxy-2-methylbenzoyl)amino]-8-azabicyclo[3.2.1]oct-8-yl]pyridine-3-carboxamide
-
-
N-[4-(3H-imidazo[4,5-c]pyridin-2-yl)-9H-fluoren-9-yl]quinoline-5-carboxamide
-
-
N-[4-(aminosulfonothioyl)benzyl]-3-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazole-4-carboxamide
N-[4-hydroxy-3-(2-hydroxynaphthalen-1-yl)phenyl]thiophene-2-sulfonamide
-
-
NaCl
-
approx. 50% inhibition at 100 mM, approx. 90% inhibition at 600 mM
NVP-AUY922
competitive inhibitor
retaspimycin hydrochloride
competitive inhibitor
Sti1
-
co-chaperone, almost complete non-competitive inhibition at a 6fold excess of Sti1 in the presence of 80 mM KCL
-
[(2R)-1-(5-chloro-2,4-dihydroxybenzoyl)pyrrolidin-2-yl](1,3-dihydro-2H-isoindol-2-yl)methanone
-
-
[1-(3-bromo-4-cyanophenyl)-2-oxo-2,4,5,6,7,7a-hexahydro-1H-indol-3-yl]acetic acid
-
-
[2,4-dihydroxy-5-(propan-2-yl)phenyl](5-[[methyl(piperidin-1-yl)amino]methyl]-1,3-dihydro-2H-isoindol-2-yl)methanone
-
AT-13387
[4-[(2S)-1-(5-chloro-2,4-dihydroxybenzoyl)pyrrolidin-2-yl]phenyl](3,3-difluoropyrrolidin-1-yl)methanone
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-6-([[(dimethylamino)acetyl]oxy]imino)-9,11-dihydroxy-14-methyl-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-6-([[(dimethylamino)acetyl]oxy]imino)-9,11-dihydroxy-14-methyl-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-14-methyl-6-(methylimino)-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-14-methyl-6-(methylimino)-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-14-methyl-6-[[(piperidin-1-ylcarbonyl)oxy]imino]-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-14-methyl-6-[[(piperidin-1-ylcarbonyl)oxy]imino]-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
-
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-6-(hydroxyimino)-14-methyl-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
KF25706
(1aR,2Z,4E,6Z,14R,15aR)-8-chloro-9,11-dihydroxy-6-(hydroxyimino)-14-methyl-1a,6,7,14,15,15a-hexahydro-12H-oxireno[e][2]benzoxacyclotetradecin-12-one
-
KF25706
(3S)-14,16-dihydroxy-3-methyl-3,4,5,6,9,10,11,12-octahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
-
-
(3S)-14,16-dihydroxy-3-methyl-3,4,5,6,9,10,11,12-octahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
-
-
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[(4-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]benzoyl)amino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
-
-
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[(4-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]benzoyl)amino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
-
-
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[(4-[[benzyl(ethyl)amino]methyl]benzoyl)amino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
-
-
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[(4-[[benzyl(ethyl)amino]methyl]benzoyl)amino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
-
-
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-(carbamoyloxy)-13,20,22-trihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3-oxo-N-(prop-2-en-1-yl)-2-azabicyclo[16.3.1]docosa-1(22),4,6,10,18,20-hexaen-19-aminium chloride
-
IPI-504
(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-(carbamoyloxy)-13,20,22-trihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3-oxo-N-(prop-2-en-1-yl)-2-azabicyclo[16.3.1]docosa-1(22),4,6,10,18,20-hexaen-19-aminium chloride
-
IPI-504
(4E,8S,9S,10E,12S,13R,14S,16R)-13,20-dihydroxy-8,14-dimethoxy-10,12,16-trimethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(22),4,10,18,20-pentaen-9-yl carbamate
-
KOSN1559
(4E,8S,9S,10E,12S,13R,14S,16R)-13,20-dihydroxy-8,14-dimethoxy-10,12,16-trimethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(22),4,10,18,20-pentaen-9-yl carbamate
-
KOSN1559
17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin
-
-
17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin
-
-
2,5-dichloro-N-[4-hydroxy-3-(2-hydroxynaphthalen-1-yl)phenyl]benzenesulfonamide
-
-
2,5-dichloro-N-[4-hydroxy-3-(2-hydroxynaphthalen-1-yl)phenyl]benzenesulfonamide
-
-
2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]-9-[3-(propan-2-ylamino)propyl]-9H-purin-6-amine
-
PU-DZ8
2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]-9-[3-(propan-2-ylamino)propyl]-9H-purin-6-amine
-
-
2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]-9-[3-(propan-2-ylamino)propyl]-9H-purin-6-amine
-
PU-DZ8
2-[(E)-2-(2-hydroxy-3-methoxyphenyl)ethenyl]-3-(4-methoxyphenyl)quinazolin-4(3H)-one
-
micromolar inhibitor
2-[(E)-2-(2-hydroxy-3-methoxyphenyl)ethenyl]-3-(4-methoxyphenyl)quinazolin-4(3H)-one
-
micromolar inhibitor
3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide
-
VER-49009
3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide
-
VER-49009
3-[(E)-[2-[(2-amino-6-methylpyrimidin-4-yl)ethynyl]benzylidene]amino]-1,3-oxazolidin-2-one
-
-
3-[(E)-[2-[(2-amino-6-methylpyrimidin-4-yl)ethynyl]benzylidene]amino]-1,3-oxazolidin-2-one
-
-
4-(1,3-benzodioxol-5-yl)-3-(5-ethyl-2,4-dihydroxyphenyl)-1H-pyrazole-5-carboxylic acid
-
G3129
4-(1,3-benzodioxol-5-yl)-3-(5-ethyl-2,4-dihydroxyphenyl)-1H-pyrazole-5-carboxylic acid
-
G3129
4-chloro-6-(4-[4-[4-(methylsulfonyl)benzyl]piperazin-1-yl]-1H-pyrazol-3-yl)benzene-1,3-diol
-
-
4-chloro-6-(4-[4-[4-(methylsulfonyl)benzyl]piperazin-1-yl]-1H-pyrazol-3-yl)benzene-1,3-diol
-
-
4-chloro-6-(5-[[2-(morpholin-4-yl)ethyl]amino]-1,2-benzoxazol-3-yl)benzene-1,3-diol
-
-
4-chloro-6-(5-[[2-(morpholin-4-yl)ethyl]amino]-1,2-benzoxazol-3-yl)benzene-1,3-diol
-
-
4-chloro-6-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
-
CCT072440
4-chloro-6-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
-
CCT072440
4-ethyl-6-[4-(1H-imidazol-4-yl)-1H-pyrazol-3-yl]benzene-1,3-diol
-
G3130
4-ethyl-6-[4-(1H-imidazol-4-yl)-1H-pyrazol-3-yl]benzene-1,3-diol
-
G3130
4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-methyl-1H-pyrazol-3-yl]-6-ethylbenzene-1,3-diol
-
CCT08159/RBT0028535
4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-methyl-1H-pyrazol-3-yl]-6-ethylbenzene-1,3-diol
-
CCT08159/RBT0028535
4-[4-(2-methyl-1,3-thiazol-4-yl)-5-(trifluoromethyl)-1,2-oxazol-3-yl]benzene-1,3-diol
-
micromolar inhibitor
4-[4-(2-methyl-1,3-thiazol-4-yl)-5-(trifluoromethyl)-1,2-oxazol-3-yl]benzene-1,3-diol
-
micromolar inhibitor
4-[4-(4-benzylpiperazin-1-yl)-1H-pyrazol-3-yl]-6-chlorobenzene-1,3-diol
-
-
4-[4-(4-benzylpiperazin-1-yl)-1H-pyrazol-3-yl]-6-chlorobenzene-1,3-diol
-
-
4-[4-(diethylamino)phenyl]-5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-1,2-oxazole-3-carboxamide
-
-
4-[4-(diethylamino)phenyl]-5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-1,2-oxazole-3-carboxamide
-
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
VER-50589
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
-
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)-1,2-oxazole-3-carboxamide
-
VER-50589
5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-4-[4-(morpholin-4-yl)phenyl]-1,2-oxazole-3-carboxamide
-
VER-52296/NVP-AUY922
5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-4-[4-(morpholin-4-yl)phenyl]-1,2-oxazole-3-carboxamide
-
NVP-AUY922
5-[2,4-dihydroxy-5-(propan-2-yl)phenyl]-N-ethyl-4-[4-(morpholin-4-yl)phenyl]-1,2-oxazole-3-carboxamide
-
VER-52296/NVP-AUY922
6-chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine
-
-
6-chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine
-
CNF-2024/BIIB021
6-chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine
-
-
6-chloro-9-[(5-methoxy-4,6-dimethylpyridin-3-yl)methyl]-9H-purin-2-amine
-
-
6-chloro-9-[(5-methoxy-4,6-dimethylpyridin-3-yl)methyl]-9H-purin-2-amine
-
-
8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-(pent-4-yn-1-yl)-9H-purin-6-amine
-
PU24FCl
8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-(pent-4-yn-1-yl)-9H-purin-6-amine
-
PU24FCl
8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9-(pent-4-yn-1-yl)-9H-purin-6-amine
-
-
8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9-(pent-4-yn-1-yl)-9H-purin-6-amine
-
-
8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-(pent-4-yn-1-yl)-9H-purin-6-amine
-
potent Hsp90 binder
8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-(pent-4-yn-1-yl)-9H-purin-6-amine
-
potent Hsp90 binder
8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]-9H-purin-6-amine
-
PU-H71
8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]-9H-purin-6-amine
-
PU-H71
8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9-[2-(cyclopropylamino)ethyl]-9H-purin-6-amine
-
-
8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9-[2-(cyclopropylamino)ethyl]-9H-purin-6-amine
-
-
8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9-[2-[(2,2-dimethylpropyl)amino]ethyl]-9H-purin-6-amine
-
-
8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9-[2-[(2,2-dimethylpropyl)amino]ethyl]-9H-purin-6-amine
-
-
9-butyl-8-(3,4,5-trimethoxybenzyl)-9H-purin-6-amine
-
PU3
9-butyl-8-(3,4,5-trimethoxybenzyl)-9H-purin-6-amine
-
PU3
9-butyl-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9H-purin-6-amine
-
-
9-butyl-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9H-purin-6-amine
-
-
9-[2-(tert-butylamino)ethyl]-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine
-
-
9-[2-(tert-butylamino)ethyl]-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine
-
-
9-[3-(tert-butylamino)propyl]-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine
-
-
9-[3-(tert-butylamino)propyl]-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine
-
-
ADP
-
-
ADP
-
complete loss of enzyme ATPase activity is seen at 0.5 mM ADP. Under saturating levels of ATP (5 mM), the enzyme loses more than 80% of its ATPase activity upon addition of as low a concentration as 0.25 mM ADP
cycloproparadicicol
-
-
desmethoxy-geldanamycin
-
-
desmethoxy-geldanamycin
-
-
diethyl (2-[6-amino-8-[(7-bromo[1,3]thiazolo[4,5-c]pyridin-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
-
-
diethyl (2-[6-amino-8-[(7-bromo[1,3]thiazolo[4,5-c]pyridin-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
-
-
diethyl (2-[6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
-
-
diethyl (2-[6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
-
-
diethyl (2-[6-amino-8-[(7-chloro[1,3]thiazolo[4,5-c]pyridin-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
-
-
diethyl (2-[6-amino-8-[(7-chloro[1,3]thiazolo[4,5-c]pyridin-2-yl)sulfanyl]-9H-purin-9-yl]ethyl)phosphonate
-
-
geldanamycin
a competitive inhibitor of Hsp90 that binds to the ATP-binding pocket in the N-terminal domain of Hsp90 with a higher affinity than ATP, binding kinetics, overview
geldanamycin
-
inhibits hsp90 function in vitro at low micromolar concentrations via the interaction with the N-terminal ATP-binding domain of Hsp90, which results in destabilization of oncogenic client proteins via the proteasomal degradation pathway
geldanamycin
-
0.002 mM, 51% inhibition, 0.005 mM, 50% inhibition
goniothalamin
-
a naturally occurring styryl-lactone, that increases both Km and kcat of Hsp90, it binds to the N-terminal domain of Hsp90 activates its ATPase activity, while inhibiting the chaperone function of Hsp90
goniothalamin
-
inhibits the chaperone activity of the enzyme Hsp90
goniothalamin
-
a naturally occurring styryl-lactone, isolated from the air-dried bark of Goniothalamus tapis Miq., that increases both Km and kcat of Hsp90. Goniothalamin binds to the N-terminal domain of HtpG. Goniothalamin does not influence the interaction of HtpG with a non-native protein or the anti-aggregation activity of HtpG significantly. But it inhibits the activity of HtpG that assists refolding of a non-native protein in cooperation with the Hsp70 chaperone system. Goniothalamin does not inhibit the refolding assisted by the DnaK chaperone system indicating that goniothalamin exerts an inhibitory effect only on the HtpG-assisted refolding process
goniothalamin
-
inhibits the chaperone activity of the enzyme Hsp90
N-(4-acetylphenyl)-3-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazole-4-carboxamide
-
-
N-(4-acetylphenyl)-3-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazole-4-carboxamide
-
-
N-[4-(aminosulfonothioyl)benzyl]-3-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazole-4-carboxamide
-
-
N-[4-(aminosulfonothioyl)benzyl]-3-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazole-4-carboxamide
-
-
p23 protein
-
cochaperone, interacts with Hsp90 in both the absence and presence of nucleotide, with a higher affinity in presence of the ATP analogue 5'-adenylyl-beta,gamma-imidodiphosphate. Mixed inhibition, one p23 binds to each subunit of the Hsp90 dimer. Complex formation between Hsp90 and p23 increases the apparent affinity of Hsp90 for 5'-adenylyl-beta,gamma-imidodiphosphate and completely inhibits the ATPase activity
-
pochonin A
-
good inhibitor of Hsp90
pochonin A
-
good inhibitor of Hsp90
pochonin D
-
nanomolar inhibitor
pochonin D
-
nanomolar inhibitor
radamide
-
-
radester
-
-
radicicol
-
and oxime drivatives
radicicol
-
nanomolar inhibitor
radicicol
-
0.002 mM, 88% inhibition, 0.0005 mM, 50% inhibition
radicicol
-
nanomolar inhibitor
radicicol
-
complete inhibition at 4 nM
additional information
coiled-coil M-domains repress ClpB activity by encircling the AAA1 ring
-
additional information
-
cochaperone GmHop-1 may play a role in Hsp90 regulation
-
additional information
-
2 further inhibitors are found in a screen with 53440 compounds
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
a highly conserved molecular chaperone of the Hsp70 family that is primarily found in the mitochondria
evolution
-
chloroplast stromal Hsp70s are believed to exist in a variety of plant species, including Arabidopsis, pea, poplar, rice, sorghum and moss
evolution
chloroplast stromal Hsp70s are believed to exist in a variety of plant species, including Arabidopsis, pea, poplar, rice, sorghum and moss
evolution
chloroplast stromal Hsp70s are believed to exist in a variety of plant species, including Arabidopsis, pea, poplar, rice, sorghum and moss
evolution
ClpB is a molecular chaperone from the AAA+ superfamily of ATPases, Hsp100 subfamily of AAA+ ATPases
evolution
-
enzyme PnHSP70 gene belongs to the HSP70 family
evolution
the enzyme belongs to the class 1 Clp AAA1 proteins of the superfamily of AAA+ proteins harboring signature Walker A and B motifs
evolution
-
the structural organization and the molecular mechanism of Hsp70 chaperones are well conserved
malfunction
ablation or inactivation of HSP101/ClpB2 in parasites results in the nearly complete block in export with substrates accumulating in the vacuole;33 furthermore this blockade affects all classes of exported proteins, whether they harbor a PEXEL motif or not
malfunction
-
depletion of mtHsp40 leads tokDNA loss
malfunction
-
depletion of mtHsp70 leads tokDNA loss
malfunction
in vivo deregulation of mortalin expression and/or function is correlated with agerelated diseases and certain cancers due to its interaction with the p53 protein
malfunction
inhibition of Hsp90 by geldanamycin disrupts substrate maturation, leading to derailment of many cellular pathways and, ultimately, cell death
malfunction
intercalation of ATPase defective subunits into the hexamer every other subunit hampers its ATPase and disaggregation activities
malfunction
the Arabidopsis Hsp70 knockout mutant cpshsc70-1 shows that stromal Hsp70 is important for the import of both photosynthetic and non-photosynthetic precursor proteins, especially at early developmental stages
malfunction
the Arabidopsis Hsp70 knockout mutant cpshsc70-2 shows that stromal Hsp70 is important for the import of both photosynthetic and non-photosynthetic precursor proteins, especially at early developmental stages
malfunction
substrate-triggered decrease in cooperativity of mutant ClpB-K476C ATPase activity. The K476C mutation weakens the dynamic interaction between M-domain and AAA1 ring resulting in M-domain dissociation and persistent, Hsp70-independent derepression of ClpB ATPase activity. Consequently, the ATPase activation by substrate is much stronger than in wild-type ClpB, and mutant ClpB-K476C has increased protein disaggregation activity, linked to its ability to unfold stable domains, an activity not observed for wild-type ClpB. ATP concentrations at half-maximal ATP hydrolysis rates of ClpB-K476C drop to 1.4 mM in the presence of substrate, compared with 4.3 mM for wild-type ClpB in the presence of substrate indicating that only the fully two-step activated state of ClpB reaches high ATPase activity at physiological ATP concentrations, which coincides with decreased cooperativity. Substrate-bound ClpB-K476C structures reveal large displacements of AAA2 pore loops. Comparisons of substrate binding structures of wild-type and mutant enzymes, overview
malfunction
-
inhibition of Hsp90 by geldanamycin disrupts substrate maturation, leading to derailment of many cellular pathways and, ultimately, cell death
-
metabolism
-
Hsc70 plays a crucial role in degradation of mutant CFTR by the ubiquitin-proteasome system. The small molecule apoptozole has high cellular potency to promote membrane trafficking of mutant DeltaF508 and its chloride channel activity in cystic fibrosis cells. Apoptozole inhibits the ATPase activity of Hsc70 by binding to its ATPase domain and apoptozole suppresses ubiquitination of DeltaF508 maybe by blocking interaction of the mutant with Hsc70 and E3 ubiquitin ligase CHIP, and, as a consequence, it enhances membrane trafficking of the mutant
metabolism
-
iron-sulfur cluster biosynthesis involves a scaffold protein (ISCU), cysteine desulfurase (NFS1), chaperone (mtHSP70), and co-chaperone (HSC20). The ATPase activity of mtHSP70 is accelerated by ch-chaperone HSC20 and further accelerated by HSC20 plus scaffold protein ISCU. mtHSP70 binds preferentially to the D-state of ISCU and that HSC20 binds preferentially to the S-state of ISCU
metabolism
-
several chaperones and cochaperones mediate different stages of chloroplast import of preproteins, which are in a largely unfolded state. Cytosolic factors such as Hsp90, Hsp70 and 14-3-3 may assist preproteins to reach the TOC complex, i.e. translocon at the outer envelope membrane of chloroplasts complex, at the chloroplast surface, preventing their aggregation or degradation. Chaperones may also be involved in the intermembrane space transport. Preprotein translocation is completed at the trans side of the inner membrane by ATP-driven motor complexes. A stromal Hsp100-type chaperone, Hsp93, cooperates with Tic110 and Tic40 in one such motor complex, while stromal Hsp70 is proposed to act in a second, parallel complex. Upon arrival in the stroma, chaperones (e.g., Hsp70, Cpn60, cpSRP43) also contribute to the folding, assembly or onward intraorganellar guidance of the proteins. Chaperone involvement in the stroma during chloroplast protein import, modeling, detailed overview
metabolism
several chaperones and cochaperones mediate different stages of chloroplast import of preproteins, which are in a largely unfolded state. Cytosolic factors such as Hsp90, Hsp70 and 14-3-3 may assist preproteins to reach the TOC complex, i.e. translocon at the outer envelope membrane of chloroplasts complex, at the chloroplast surface, preventing their aggregation or degradation. Chaperones may also be involved in the intermembrane space transport. Preprotein translocation is completed at the trans side of the inner membrane by ATP-driven motor complexes. A stromal Hsp100-type chaperone, Hsp93, cooperates with Tic110 and Tic40 in one such motor complex, while stromal Hsp70 is proposed to act in a second, parallel complex. Upon arrival in the stroma, chaperones (e.g., Hsp70, Cpn60, cpSRP43) also contribute to the folding, assembly or onward intraorganellar guidance of the proteins. Chaperone involvement in the stroma during chloroplast protein import, modeling, detailed overview
metabolism
several chaperones and cochaperones mediate different stages of chloroplast import of preproteins, which are in a largely unfolded state. Cytosolic factors such as Hsp90, Hsp70 and 14-3-3 may assist preproteins to reach the TOC complex, i.e. translocon at the outer envelope membrane of chloroplasts complex, at the chloroplast surface, preventing their aggregation or degradation. Chaperones may also be involved in the intermembrane space transport. Preprotein translocation is completed at the trans side of the inner membrane by ATP-driven motor complexes. A stromal Hsp100-type chaperone, Hsp93, cooperates with Tic110 and Tic40 in one such motor complex, while stromal Hsp70 is proposed to act in a second, parallel complex. Upon arrival in the stroma, chaperones (e.g., Hsp70, Cpn60, cpSRP43) also contribute to the folding, assembly or onward intraorganellar guidance of the proteins. Chaperone involvement in the stroma during chloroplast protein import, modeling, detailed overview
metabolism
-
ClpB interacts differently with DnaK in the presence of aggregates or small peptides, displaying a higher affinity for aggregate-bound DnaK. DnaK-ClpB collaboration requires the coupled ATPase-dependent remodeling activities of both chaperones
metabolism
-
the enzyme ClpB disaggregates and reactivates aggregated proteins in cooperation with the Hsp70/Hsp40 chaperones DnaK, DnaJ, and GrpE. The substrate recognition mechanism of ClpB relies on global surface properties of aggregated proteins
metabolism
the enzyme is implicated in the assembly of EPK protein kinases, bHlH transcription factors, nuclear hormone receptors, SCF ubiquitin ligases, RNA polymerases, PI3-kinase-like kinases such as mTOR and SMG1, snoRNPs8 and Nod-like innate immunity receptors
metabolism
-
the enzyme requires ATP hydrolysis to favor the native folding of its substrates and, under stress, to avoid aggregation and revert misfolding
metabolism
the Hsp90 chaperone is a central node of protein homeostasis activating a large number of diverse client proteins. Hsp90 functions as a molecular clamp that closes and opens in response to the binding and hydrolysis of ATP
physiological function
-
Hsp90 functions in quality control in the cell. The enzyme does not participate in primary protein folding events, but rather its function is restricted to the posttranslational maturation and disposition of a relatively limited subset of conformationally labile client proteins (i.e. Her2, Raf-1, Akt, Cdk4, Polo-1 kinase, cMet, mutant B-Raf, mutant p53, AR, ER, Bcr-Abl, HIF-1 alpha, hTERT)
physiological function
-
Hsp90 functions in quality control in the cell. The enzyme does not participate in primary protein folding events, but rather its function is restricted to the posttranslational maturation and disposition of a relatively limited subset of conformationally labile client proteins (i.e. Her2, Raf-1, Akt, Cdk4, Polo-1 kinase, cMet, mutant B-Raf, mutant p53, AR, ER, Bcr-Abl, HIF-1 alpha, hTERT)
physiological function
-
HSP90 is involved in the proper folding or refolding of approximately 200 client proteins
physiological function
ClpB is a molecular chaperone, which reactivates aggregated proteins in cooperation with the DnaK chaperone system. ClpB is essential for infectivity and in-host survival. The chaperone activity of PfClpB1 may support survival of Plasmodium falciparum by maintaining the folding status and activity of apicoplast proteins. The ATP hydrolysis-driven reactivation of aggregates mediated by ClpB is linked to substrate translocation through the narrow central pore in the hexameric assembly
physiological function
ClpB proteins function as unfoldases and disaggregases. ClpB1 is present in the apicoplast, a parasite-specific and plastid-like organelle hosting various metabolic pathways necessary for parasite growth. Molecular chaperones appear to play important roles in keeping parasite proteins in a translocation competent state prior to crossing the parasitophorous vacuole membrane
physiological function
ClpB proteins function as unfoldases and disaggregases. ClpB2 localizes to the parasitophorous vacuole membrane where it drives protein export as core subunit of a parasite-derived protein secretion complex, the Plasmodium translocon of exported proteins (PTEX), this process is central to parasite virulence and survival in the human host. Molecular chaperones appear to play important roles in keeping parasite proteins in a translocation competent state prior to crossing the parasitophorous vacuole membrane. ClpB2/HSP101 is essential to the organism and actively drives the export process by harnessing the energy from ATP hydrolysis to unfold and thread the diverse cargos through the trans-membrane conduit EXP2
physiological function
co-chaperones help to maintain cellular homeostasis by modulating the activities of molecular chaperones involved in protein quality control. The HSP70/HSP90-organizing protein (HOP) is a co-chaperone that cooperates with HSP70 and HSP90 in catalysis of protein folding and maturation in the cytosol. HOP has ATP-binding activity comparable to that of HSP70/HSP90, and that HOP slowly hydrolyzes ATP. The ATPase domain of HOP locates in the N-terminal TPR1-DP1-TPR2A segment. HOP changes its conformation in the presence of ATP, its ATPase activity is unaffected by the D186A mutation
physiological function
dependence of Entamoeba histolytica on Hsp90 for its growth and survival. Hsp90 plays a critical role in manifestation of infection by virulent human and animal pathogens. Hsp90 function is regulated by various co-chaperones, e.g. by co-chaperone Aha1 (activator of Hsp90 ATPase), EhAha1c, lacking a canonical Aha1 N-terminal domain. These proteins can regulate Hsp90 in multiple ways either by regulating the ATPase activity, by priming it to interact with a certain client group, by assisting in formation of a multichaperone complex, or by aidingin client maturation
physiological function
heat shock protein 70 is a molecular chaperone that plays an important role in protein folding and transport. It is also involved in regulation of innate and adaptive immune response. PoHsp70 is an effective adjuvant and that the adjuvanticity of PoHsp70 requires the intrinsic ATPase activity
physiological function
Hsp70 is involved in te chloroplast import of preproteins. It may form a guidance complex together with 14-3-3 that delivers phosphorylated preproteins to the Toc34 receptor. Hsp70 is also proposed to deliver preproteins to the OEP61 protein
physiological function
-
Hsp70 is involved in te chloroplast import of preproteins. Stromal Hsp70 might provide the driving force in chloroplast protein import
physiological function
Hsp70 is involved in te chloroplast import of preproteins. Stromal Hsp70 might provide the driving force in chloroplast protein import
physiological function
Hsp70 is involved in te chloroplast import of preproteins. Stromal Hsp70 might provide the driving force in chloroplast protein import. It may form a guidance complex together with 14-3-3 that delivers phosphorylated preproteins to the Toc34 receptor. Hsp70 is also proposed to deliver preproteins to the OEP61 protein
physiological function
Hsp70 is involved in the chloroplast import of preproteins. Stromal Hsp70 might provide the driving force in chloroplast protein import
physiological function
-
Hsp90 is an ATP-dependent molecular chaperone that is involved in important cellular pathways such as signal transduction pathways. The Hsp90 ATPase activity may facilitate elucidation of the chaperone mechanism of Hsp90
physiological function
-
Hsp90 is an ATP-dependent molecular chaperone that is involved in important cellular pathways such as signal transduction pathways. The Hsp90 ATPase activity may facilitate elucidation of the chaperone mechanism of Hsp90
physiological function
-
Hsp90 is part of a family of molecular chaperones that play a crucial role in the normal folding, intracellular disposition, and proteolytic turnover of a vast array of factors involved in cell regulation. The Hsp90 protein folding activity is ATP-dependent and ATP hydrolysis is a key aspect in the Hsp90 chaperone function. Increase of Hsp90 expression and activity has been linked with the protection of oncoproteins from physiological clearance
physiological function
-
mitochondrial chaperone PnHSP70 might play an important role in the adaptation of the antarctic moss Pohlia nutans to the polar environment
physiological function
the ClpB hexamer hydrolyzes ATP and reactivates protein aggregates. ClpB cooperatively hydrolyzes ATP, and this cooperativity is crucial for protein disaggregation. Subunit D1 and D2 dimers have the essential properties of TClpB, evaluation of intersubunit cooperativity, overview
physiological function
the enzyme is of considerable importance for mitochondria biogenesis and the correct functioning of the cell machinery. In the mitochondrial matrix, mortalin acts in the importing and folding process of nucleus-encoded proteins, mortalin is the import motor that drives the preprotein import process and helps the folding of these proteins in the mitochondrial matrix. Depending on its localization and its binding partners, mortalin is associated with several functions, overview
physiological function
-
the enzyme promotes the folding of proteins mainly in the mitochondrial matrix. Another fraction of mtHsp70 is associated with the translocation channel of the TIM23 translocase on the matrix side of the inner membrane and functions as a central component of the import motor of the translocase
physiological function
-
the highly conserved mitochondrial chaperone machinery, essential for proper functioning of mitochondria, is composed of mitochondrial heat shock proteins 70 and 40 (mtHsp70/mtHsp40) and the ATP exchange factor Mge1. The chaperones are indispensable for the maintenance and replication of kDNA, in addition to their already known functions in Fe-S cluster synthesis and protein import
physiological function
-
the Hsp70 family of molecular chaperones assists in protein folding, degradation, assembly/disassembly of some complexes, and intracellular trafficking. These activities in the cell are accomplished by coupled conformational switches/signals between their nucleotide-binding and substrate-binding domains (NBD and SBD), assisted by cognate co-chaperones
physiological function
-
the enzyme is essential for bacterial survival under stressful conditions and also during infection. The enzyme activates the host immune system
physiological function
-
the enzyme is required for thermotolerance and function in disaggregation and reactivation of aggregated proteins that form during severe stress conditions
physiological function
the enzyme is required for thermotolerance and function in disaggregation and reactivation of aggregated proteins that form during severe stress conditions
physiological function
-
the enzyme reactivates aggregated proteins in cooperation with the DnaK chaperone system and promotes survival of bacteria under stress conditions. The enzyme can support the virulence of Leptospira interrogans by protecting the conformational integrity and catalytic activity of multiple metabolic enzymes, thus maintaining energy homeostasis in pathogen cells
physiological function
-
the enzyme's importance during infection is due to its role as a molecular chaperone involved in reactivation of protein aggregates
physiological function
-
the enzyme's importance during infection is due to its role as a molecular chaperone involved in reactivation of protein aggregates
physiological function
-
dependence of Entamoeba histolytica on Hsp90 for its growth and survival. Hsp90 plays a critical role in manifestation of infection by virulent human and animal pathogens. Hsp90 function is regulated by various co-chaperones, e.g. by co-chaperone Aha1 (activator of Hsp90 ATPase), EhAha1c, lacking a canonical Aha1 N-terminal domain. These proteins can regulate Hsp90 in multiple ways either by regulating the ATPase activity, by priming it to interact with a certain client group, by assisting in formation of a multichaperone complex, or by aidingin client maturation
-
physiological function
-
Hsp90 is an ATP-dependent molecular chaperone that is involved in important cellular pathways such as signal transduction pathways. The Hsp90 ATPase activity may facilitate elucidation of the chaperone mechanism of Hsp90
-
physiological function
-
the enzyme reactivates aggregated proteins in cooperation with the DnaK chaperone system and promotes survival of bacteria under stress conditions. The enzyme can support the virulence of Leptospira interrogans by protecting the conformational integrity and catalytic activity of multiple metabolic enzymes, thus maintaining energy homeostasis in pathogen cells
-
additional information
all Hsp70 molecules possess a conserved architecture that consists of a 44 kDa N-terminal adenine nucleotide-binding domain (NBD), which hydrolyzes ATP and thus is also called the ATPase domain, an 18 kDa substrate-binding domain (SBD) that contains a hydrophobic pocket in which direct substrate interaction occurs, and a 10 kDa C-terminal domain (CTD) that facilitates substrate trapping by forming a lid-like structure over the substrate binding pocket. PoHsp70 possesses an ATPase domain (residues 108e433) that contains the conserved residues (D201, S210, and G341) involved in ATP binding
additional information
-
all Hsp70 molecules possess a conserved architecture that consists of a 44 kDa N-terminal adenine nucleotide-binding domain (NBD), which hydrolyzes ATP and thus is also called the ATPase domain, an 18 kDa substrate-binding domain (SBD) that contains a hydrophobic pocket in which direct substrate interaction occurs, and a 10 kDa C-terminal domain (CTD) that facilitates substrate trapping by forming a lid-like structure over the substrate binding pocket. PoHsp70 possesses an ATPase domain (residues 108e433) that contains the conserved residues (D201, S210, and G341) involved in ATP binding
additional information
-
ClpB proteins share a common architecture consisting of four domains, a variable N-terminal domain that binds different protein substrates, followed by two highly conserved catalytic ATPase domains, and a C-terminal domain, structure overview. Pseudo two-fold internal symmetry creates a hydrophobic patch at the surface of the N terminal domains of the two ClpB chaperones from Plasmodium
additional information
ClpB proteins share a common architecture consisting of four domains, a variable N-terminal domain that binds different protein substrates, followed by two highly conserved catalytic ATPase domains, and a C-terminal domain, structure overview. Pseudo two-fold internal symmetry creates a hydrophobic patch at the surface of the N terminal domains of the two ClpB chaperones from Plasmodium
additional information
-
conformational changes in human Hsp70 induced by high hydrostatic pressure produce oligomers with ATPase activity but without chaperone activity
additional information
distribution of co-chaperones in Entamoeba histolytica, overview
additional information
-
distribution of co-chaperones in Entamoeba histolytica, overview
additional information
each monomer of the hexameric enzyme containing four domains: an N-terminal domain, which improves the reactivation efficiency of stable protein aggregates, connected to the rest of the protein by a conserved linker, two nucleotide-binding domains (NBD1 and NBD2) that bind and hydrolyse ATP, and a middle (M) domain. The M domain, which is specific for ClpB and its homologues, is inserted into the NBD1, folds as a coiled-coil structure built up by four helices and is strictly required for the disaggregase activity of the chaperone. ClpB dynamics is modulated by the DnaK system and substrate proteins, effect of the N-terminal and M domains on ClpB dynamics, overview. The substrate-binding domain of DnaK regulates ClpB dynamics
additional information
-
identification of a network of conserved interactions in subdomain IA of the nucleotide-binding domain, which plays a key (effector) role in propagating signals between the ATP-binding and substrate-binding sites. Subdomain IIA, on the other hand, appears to adapt to J-domain co-chaperone binding by virtue of a broadly distributed cluster of co-evolving residues on the recognition surface. L177 plays a key role in conveying signals from the linker and DnaJ-binding site to the ATP-binding site. V389 exhibits a strong co-variance with L177, a hydrophobic residue at the linker-binding pocket. L177, in turn, is highly correlated with I373, another hydrophobic residue in the vicinity of the linker-binding pocket. Nucleotide-binding domain subdomain IA, and in particular a number of highly conserved (V139, D148, K155, R167, N170, E171) or co-evolving (R159, L177) residues therein, serve as mediators of communication between the substrate- and nucleotide-binding sites of the respective SBD and NBD, in addition to their involvement in relaying signals from the DnaJ-binding site to the ATP-binding site. Residues involved in co-chaperone recognition and their coupling to the NBD-SBD interfacial region, overview
additional information
-
isoform Hsp70-1 cannot substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
isoform Hsp70-1 cannot substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
isoform Hsp70-1 cannot substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
-
isoform Hsp70-3 cannot substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
isoform Hsp70-3 cannot substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
isoform Hsp70-3 cannot substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
-
isolated chloroplasts containing the temperature-sensitive Hsp70-2 protein display lower import competence after heat-shock treatment, when compared with wild-type chloroplasts. Neither of the other two isoforms, Hsp70-1 and Hsp70-3, can substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
isolated chloroplasts containing the temperature-sensitive Hsp70-2 protein display lower import competence after heat-shock treatment, when compared with wild-type chloroplasts. Neither of the other two isoforms, Hsp70-1 and Hsp70-3, can substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
isolated chloroplasts containing the temperature-sensitive Hsp70-2 protein display lower import competence after heat-shock treatment, when compared with wild-type chloroplasts. Neither of the other two isoforms, Hsp70-1 and Hsp70-3, can substitute the loss of Hsp70-2 despite their high degree of similarity
additional information
mortalin is formed by at least two domains, the transition is sensitive to the presence of adenosine nucleotides and the process is dependent on the presence of Mg2+ ions. Thermal-induced unfolding assays of mortalin suggest the presence of an aggregation/association event, which may explain its natural tendency for in vivo aggregation
additional information
-
mortalin is formed by at least two domains, the transition is sensitive to the presence of adenosine nucleotides and the process is dependent on the presence of Mg2+ ions. Thermal-induced unfolding assays of mortalin suggest the presence of an aggregation/association event, which may explain its natural tendency for in vivo aggregation
additional information
the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring is sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. Protein disaggregation activities of wild-type and cross-linked enzyme TClpB in cooperation with TDnaK system
additional information
-
the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring is sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. Protein disaggregation activities of wild-type and cross-linked enzyme TClpB in cooperation with TDnaK system
additional information
the enzyme structure contains two highly-conserved ATP-binding modules D1 and D2, the N-terminal domain, and the middle domain. The nucleotide-binding Walker A/B and sensor-1/-2 motifs as well as the substrate-binding pore motifs are present in the sequence, the N-terminal leader sequences that specify their cellular localization, and the endoplasmic reticulum-targeting signal sequence with the predicted signal peptide cleavage between Ser23 and Lys24 in PfClpB1. PfClpB1 also contains a 120-residue long predominantly basic, K- and N-rich segment, which is a predictor of an apicoplast-targeting sequence
additional information
-
the enzyme structure contains two highly-conserved ATP-binding modules D1 and D2, the N-terminal domain, and the middle domain. The nucleotide-binding Walker A/B and sensor-1/-2 motifs as well as the substrate-binding pore motifs are present in the sequence, the N-terminal leader sequences that specify their cellular localization, and the endoplasmic reticulum-targeting signal sequence with the predicted signal peptide cleavage between Ser23 and Lys24 in PfClpB1. PfClpB1 also contains a 120-residue long predominantly basic, K- and N-rich segment, which is a predictor of an apicoplast-targeting sequence
additional information
-
the N-terminal ATPase domain is connected via a short hydrophobic interdomain linker to a C-terminal peptide-binding domain. The interdomain linker between the ATPase domain and PBD is required for the communication between both domains and affects the native conformation of the ATPase domain
additional information
disaggregase ClpB contains tandem ATPase domains (AAA1, AAA2) and shifts between low and high ATPase and threading activities. Coiled-coil M-domains repress ClpB activity by encircling the AAA1 ring. ClpB activation reduces ATPase cooperativity and induces a sequential mode of ATP hydrolysis in the AAA2 ring, the main ATPase motor. AAA1 and AAA2 rings do not work synchronously but in alternating cycles. This ensures high grip, enabling substrate threading via a processive, rope-climbing mechanism. Residue Lys476 is part of a conserved salt bridge network that regulates the dynamic interaction between M-domain and AAA1 ring. Comparisons of substrate binding structures of wild-type and mutant enzymes, overview
additional information
-
distribution of co-chaperones in Entamoeba histolytica, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
V431F
-
mutant is unable to suppress the thermosensitivity of an Escherichia coli dnak103 deletion strain. Mutant is able to prevent the thermal aggregation of malate dehydrogenase
D526A
-
the DnaK mutant is unable to render a stimulated bichaperone complex with ClpB and doe s not reactivate glucose-6-phosphate dehydrogenase aggregates
E12C
-
C for fluorescent labelling
E12C/C-terminal truncation
-
containing residue 1-496, monomeric
E12C/E34A
-
mutant hydrolyses ATP about 10-times more slowly than wild-type protein, C for fluorescent labelling
E274A/E678A
-
inactive ClpB mutant
E279A/K476C/E678A
site-directed mutagenesis, the mutant shows a reduced number of subunits
E279Q/E678Q
-
ATP-hydrolysis deficient substrate-trapping variant
E34A
-
mutant hydrolyses ATP about 10-times more slowly than wild-type protein
F105W/W462F/W543F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
F276W/W462F/W543F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
F603W/W462F/W543F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
K476C
site-directed mutagenesis, the mutation weakens the dynamic interaction between M-domain and AAA1 ring resulting in M-domain dissociation and persistent, Hsp70-independent derepression of ClpB ATPase activity. Consequently, the ATPase activation by substrate is much stronger than in wild-type ClpB, and mutant ClpB-K476C has increased protein disaggregation activity, linked to its ability to unfold stable domains, an activity not observed for wild-type ClpB. ATP concentrations at half-maximal ATP hydrolysis rates of ClpB-K476C drop to 1.4 mM in the presence of substrate, compared with 4.3 mM for wild-type ClpB in the presence of substrate indicating that only the fully two-step activated state of ClpB reaches high ATPase activity at physiological ATP concentrations, which coincides with decreased cooperativity. Substrate-bound ClpB-K476C structures reveal large displacements of AAA2 pore loops
K70A
-
the DnaK mutant shows impaired ATP hydrolysis activity
T199A
-
the DnaK mutant shows impaired ATP hydrolysis activity
T213N
-
mutation in Walker A motif
T213N/T612N
-
mutations in Walker A motif
T612N
-
mutation in Walker A motif
V210C
-
DnaK (residue 1-655), C used for spin labeling experiments
W462F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
W462F/W543F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
W543F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
Y251A/K476C
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity compared to wild-type enzyme
Y251A/K476C/Y653A
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity compared to wild-type enzyme
Y251W/W462F/W543F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
Y653A/K476C
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity compared to wild-type enzyme
Y812/W462F/W543F
-
mutant constructed for thermodynamic analysis. Similar to wild-type, variant efficiently forms oligomers at high protein concentration, and shows ATPase activity
A116N
-
reduced affinity to co-chaperone Hop in the presence of ATP analogue AMPPNP
K71E
-
no ATPase activity
T110I
-
wild-type affinity to co-chaperone Hop
E371C
site-directed mutagenesis, the chaperone activity of ClpBE731C is similar to that of the wild-type protein
S433C
site-directed mutagenesis, the chaperone activity of ClpBS433C is similar to that of the wild-type protein
S499C
site-directed mutagenesis, the mutant shows 10-20fold increased ATPase activity, the chaperone activity of mutantt ClpBS499C is 20-25% more efficient than the wild-type
A107N
the mutation increases ATPase activity about 5fold compared to the wild type
A17V
-
nucleotide-binding domain mutant
C63A
-
the ATPase activity displayed by the unmodified ATPase domain Kar2 is fully maintained when Cys63 is replaced with Ala
C63E
-
the mutant shows limited ATPase activity
C63F
-
the mutation leads to loss of ATPase activity. The mutation supports an enhanced viability during oxidative stress associated with the oxidized ATPase domain Kar2
C63H
-
the mutation supports an enhanced viability during oxidative stress associated with the oxidized ATPase domain Kar2
C63N
-
the mutant shows limited ATPase activity
C63P
-
the mutation supports an enhanced viability during oxidative stress associated with the oxidized ATPase domain Kar2
C63V
-
the ATPase activity displayed by the unmodified ATPase domain Kar2 is fully maintained when Cys63 is replaced with Val
C63W
-
the mutation leads to loss of ATPase activity. The mutation leads to loss of ATPase activity. The mutation supports an enhanced viability during oxidative stress associated with the oxidized ATPase domain Kar2
C63Y
-
the mutation leads to loss of ATPase activity. The mutation supports an enhanced viability during oxidative stress associated with the oxidized ATPase domain Kar2
D61C/Q333C
-
C used to label with fluorescent dyes
E285Q
-
impaired hydrolysis of ATP at nucleotide-binding domain 1
E285Q/E687Q
-
impaired hydrolysis of ATP at nucleotide-binding domains 1 and 2
E381K
-
no loss of ATPase activity at the non permissive temperature of 37°C
E687Q
-
impaired hydrolysis of ATP at nucleotide-binding domain 2
K199N
-
missense Sis1 mutant exhibits greatly reduced binding affinity for the Ssa1 lid domain
K202N
-
missense Sis1 mutant exhibits greatly reduced binding affinity for the Ssa1 lid domain
K214N
-
missense Sis1 mutant exhibits greatly reduced binding affinity for the Ssa1 lid domain
K620T
-
impaired binding and hydrolysis of ATP at nucleotide-binding domain 2
L483W
-
substrate-binding domain mutant
R34K
-
nucleotide-binding domain mutant
S25P
-
the mutation of Hsp82p impairs ATPase stimulation by Aha1p. The intrinsic ATPase activity of the mutant is comparable to that of wildtype enzyme
T101I
the mutation substantially reduces ATPase activity
T22F
-
increased ATP hydrolysis rate
E271Q/R576C/A821C
site-directed mutagenesis
E271Q/R576C/E668Q/A821C
site-directed mutagenesis
I403A/L406A/L413A/L420A/L432A/I439A/I446A/L449A
-
residues of hydrophobic interactions
I403A/L406A/L413A/L420A/L432A/I439A/I446A/L449A/I459A/L463A/L470A/V473A/I477A/L492A/L497A/L500A/L507A/L511A
-
residues of hydrophobic interactions
I459A/L463A/L470A/V473A/I477A/L492A/L497A/L500A/L507A/L511A
-
residues of hydrophobic interactions
K204A/T205A/R576C/A821C
site-directed mutagenesis
K204A/T205A/R576C/K601A/K602A/A821C
site-directed mutagenesis
K204Q/K601Q
-
Walker A mutant
L406A/L413A/L420A/L432A/I439A/I446A
-
residues of hydrophobic interactions
L406A/L413A/L420A/L432A/I439A/I446A/L463A/L470A/I477A/L492A/L500A/L507A
-
residues of hydrophobic interactions
L413A/L420A/L432A/I439A
-
residues of hydrophobic interactions
L413A/L420A/L432A/I439A/L470A/I477A/L492A/L500A
-
residues of hydrophobic interactions
L463A/L470A/I477A/L492A/L500A/L507A
-
residues of hydrophobic interactions
L470A/I477A/L492A/L500A
-
residues of hydrophobic interactions
Q184C/A390C
site-directed mutagenesis
Q184C/A390C/E668Q
site-directed mutagenesis
Q184C/A390C/K601A/K602A
site-directed mutagenesis
Q184C/A390C/R747A
site-directed mutagenesis
Q184C/E271Q/A390C
site-directed mutagenesis
Q184C/E271Q/A390C/E668Q
site-directed mutagenesis
Q184C/K204A/T205A/A390C
site-directed mutagenesis
Q184C/K204A/T205A/A390C/K601A/K602A
site-directed mutagenesis
Q184C/R322A/A390C
site-directed mutagenesis
R322A/R576C/A821C
site-directed mutagenesis
R576C/A821C
site-directed mutagenesis
R576C/E668Q/A821C
site-directed mutagenesis
R576C/K601A/K602A/A821C
site-directed mutagenesis
R576C/R747A/A821C
site-directed mutagenesis
S783C
-
C used to label specifically by thiol-reactive dyes
K218T
-
mutation results in complete loss of polypeptide binding
K218T
-
impaired binding and hydrolysis of ATP at nucleotide-binding domain 1
E271A/E668A
-
trap mutant, electron cryomicroscopy reconstruction
E271A/E668A
-
Walker B mutant
additional information
-
in slothu45 mutant, the initial steps in sarcomere assembly take place, but thick filaments are absent and filamentous I-Z-I brushes fail to align or adopt correct spacing. The mutation only affects skeletal muscle and mutant embryos show no other obvious phenotypes. Phenotype is due to mutation in one copy of a tandemly duplicated hsp90a gene disrupting the chaperoning function through interference with aTPase activity. Loss of Hsp90a function leads to the downregulation of genes encoding sarcomeric proteins and upregulation of hsp90a and several other genes encoding proteins that may act with Hsp90a during sarcomere assembly
additional information
-
construction of DnaK /mtHsp70 chimeras by replacing different regions of the DnaK (from Escherichia coli) peptide-binding domain with those of mtHsp70 (from Saccharomyces cerevisiae) results in chimeric proteins that: (a) are not able to support growth of an Escherichia coli DnaK deletion strain at stress temperatures (e.g. 42°C), (b) show increased accessibility and decreased thermal stability of the peptide-binding pocket, and (c) have reduced activation by bacterial, but not mitochondrial cochaperones, as compared with DnaK
additional information
-
mutations in ATPase domain D2 significantly lowers enzyme activity
additional information
-
in vitro studies demonstrate that the N terminus of HSP70 including the ATPase domain and the substrate-binding beta-subdomain is not sufficient to bind with the J domain of HSJ1a. The C-terminal helical alpha-subdomain of HSP70 (residues 562610), is crucial for binding with the J domain of HSJ1a and stimulating the ATPase activity of HSP70
additional information
a mutant PoHsp70, PoHsp70M, that bears a mutation of the ATPase-associated domain, is completely abolished in activity. Construction of the DNA vaccine plasmids with wild-type and mutant enzymes, pSia10Hsp70 and pSia10Hsp70M. pSia10Hsp70 induces a survival rate that is significantly higher than that induced by pSia10, while pSia10Hsp70M induces a survival rate similar to that induced by pSia10
additional information
-
a mutant PoHsp70, PoHsp70M, that bears a mutation of the ATPase-associated domain, is completely abolished in activity. Construction of the DNA vaccine plasmids with wild-type and mutant enzymes, pSia10Hsp70 and pSia10Hsp70M. pSia10Hsp70 induces a survival rate that is significantly higher than that induced by pSia10, while pSia10Hsp70M induces a survival rate similar to that induced by pSia10
additional information
-
consstruction of a temperature-sensitive hsp70-2 knockout mutant
additional information
consstruction of a temperature-sensitive hsp70-2 knockout mutant
additional information
consstruction of a temperature-sensitive hsp70-2 knockout mutant
additional information
deletion of the N-terminal domain activates the basal activity 2fold, whereas elimination of the M domain increases the ATPase activity 10fold in the presence of casein. Attachment of fluorescent probes in the M domain and NBD2 does not affect the activity of ClpBS433C, it decreases that of ClpBE731C, especially when labelled with Alexa Fluor 350 (3fold reduction), and severely inhibits the ClpBS499C variant, overview
additional information
-
N-terminal deletion mutant DELTA8-Hsp90 still has ATPase activity that is not inhibited by Sti1
additional information
-
construction of DnaK /mtHsp70 chimeras by replacing different regions of the DnaK (from Escherichia coli) peptide-binding domain with those of mtHsp70 (from Saccharomyces cerevisiae) results in chimeric proteins that: (a) are not able to support growth of an Escherichia coli DnaK deletion strain at stress temperatures (e.g. 42°C), (b) show increased accessibility and decreased thermal stability of the peptide-binding pocket, and (c) have reduced activation by bacterial, but not mitochondrial cochaperones, as compared with DnaK
additional information
-
identification of 25 mutations within the two major cytosolic Hsp70-SSa molecular chaperones that impair the propagation of the [PSI+] prion. All but one mutation are located within the ATPase domain, and only mutation SSA2-A176T has major effects on growth rate
additional information
-
construction of a mutant mtHsp70A4, in which the linker residues of mtHsp70 are likewise replaced by four alanine residues. This variant generates in the folding assay only a 35-kD stable fragment that corresponds in size to the peptide-binding domain, the ATPase domain in the mtHsp70A4 mutant is not able to fold into a protease-resistant form
additional information
-
construction of C-terminal truncation and amino acid replacements in the IXI/V motif leading to loss of chaperone activity of all mutants at 83°C in contrast to the wild-type enzyme, both wild type and StHsp14.0WKW exhibit almost no significant change in secondary structure at high temperatures of 85°C and 50°C. Construction of an N-terminal truncation mutants of StHsp14.0, which form stable oligomeric complexes similar to that of the wild type, but exhibits reduced chaperone activity for the protection of thermophilic IPMDH from thermal aggregation
additional information
-
construction of C-terminal truncation and amino acid replacements in the IXI/V motif leading to loss of chaperone activity of all mutants at 83°C in contrast to the wild-type enzyme, both wild type and StHsp14.0WKW exhibit almost no significant change in secondary structure at high temperatures of 85°C and 50°C. Construction of an N-terminal truncation mutants of StHsp14.0, which form stable oligomeric complexes similar to that of the wild type, but exhibits reduced chaperone activity for the protection of thermophilic IPMDH from thermal aggregation
-
additional information
-
mutant proteins show altered ATPase activities
additional information
preparation of ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately. ATPase activities of ordered heterohexamers with varyying mutations in the Walker A and B motifs, or the Arg-finger, of the two D domains, overview
additional information
-
preparation of ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately. ATPase activities of ordered heterohexamers with varyying mutations in the Walker A and B motifs, or the Arg-finger, of the two D domains, overview
additional information
-
RNAi-mediated downregulation of mtHsp40, Cells depleted for mtHsp70/mtHsp40 machinery lose kDNA but does not disrupt the cell cycle, phenotype
additional information
-
RNAi-mediated downregulation of mtHsp70, cells depleted for mtHsp70/mtHsp40 machinery lose kDNA but does not disrupt the cell cycle, phenotype
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.