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Literature summary for 2.7.11.21 extracted from
- Inhibitors of the polo-Box domain of polo-like kinase 1 (2016), ChemBioChem, 17, 650-656.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | because the polo-box domain is unique to the five-member family of polo-like kinases, and its inhibition is sufficient to inhibit the enzyme, the Plk1 PBD is an attractive target for the inhibition of Plk1 function | Homo sapiens |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| analysis of X-ray crystal structure of the Plk1 PBD (amino acids 367-603) in complex with the peptide Pro-Met-Gln-Ser-pThr-Pro-Leu, PDB ID 1UMW, the phosphopeptide binds to a shallow cleft formed between polo box 1 (PB1) and polo box 2 (PB2), which are clamped together by the Polo-cap | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (-)-epigallocatechin | - |
Homo sapiens |  |
| (1R)-1-[(3S,6S,9S,12S,15S)-19-(6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl)-3-carbamoyl-9-(hydroxymethyl)-12-(1H-imidazol-5-ylmethyl)-15-(2-methylpropyl)-5,8,11,14,17,20-hexaoxo-1-thia-4,7,10,13,16,19-hexaazacyclohenicosan-6-yl]ethyl phosphate | PL-116 | Homo sapiens | |
| (1R)-1-[(3S,6S,9S,12S,15S)-19-(6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl)-3-carbamoyl-9-(hydroxymethyl)-15-(2-methylpropyl)-5,8,11,14,17,20-hexaoxo-12-[[1-(9-phenylnonyl)-1H-imidazol-5-yl]methyl]-1-thia-4,7,10,13,16,19-hexaazacyclohenicosan-6-yl]ethyl phosphate | PL-120 | Homo sapiens | |
| (2Z)-2-(5-bromo-2-methoxybenzylidene)-6-methyl-7H-[1,3]thiazolo[3,2-b][1,2,4]triazine-3,7(2H)-dione | - |
Homo sapiens | |
| (3S)-4-amino-4-oxo-3-([[2-(4-phenylbutyl)-1-(2-phenylethyl)-1H-benzimidazol-5-yl]carbonyl]amino)butan-2-yl phosphate | - |
Homo sapiens | |
| (4E)-5-methyl-4-[[(2-methylbenzoyl)oxy]imino]-2-(propan-2-yl)cyclohexa-2,5-dien-1-one | - |
Homo sapiens | |
| (4R)-1-acetyl-4-(4-phenylbutoxy)prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threoninamide | - |
Homo sapiens | |
| (4R)-1-acetyl-4-[[(E)-(3-phenylpropylidene)amino]oxy]prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threoninamide | - |
Homo sapiens | |
| 1-(26-oxo-2,5,8,11,14,17,20,23-octaoxahexacosan-26-yl)-L-prolyl-L-leucyl-3-(8-phenyloctyl)-L-histidyl-L-seryl-(3R)-4-phosphono-L-valinamide | - |
Homo sapiens | |
| 1-acetyl-L-prolyl-L-leucyl-3-(8-phenyloctyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide | - |
Homo sapiens | |
| 1-acetyl-L-prolyl-L-leucyl-3-[3-(2-hydroxyethyl)-1-(8-phenyloctyl)-1H-imidazol-3-ium-5-yl]-L-alanyl-L-seryl-O-phosphono-L-threoninamide | - |
Homo sapiens | |
| 1-acetyl-L-prolyl-L-leucyl-3-[3-(2-hydroxyethyl)-1-(8-phenyloctyl)-1H-imidazol-3-ium-5-yl]-L-alanyl-L-seryl-O-[[[(2,2-dimethylpropanoyl)oxy]methoxy](hydroxy)phosphoryl]-L-threoninamide | - |
Homo sapiens | |
| 2,3,4,6-tetrahydroxy-5H-benzo[7]annulen-5-one | HeLa cells treated with purpurogallin exhibit delayed onset of mitosis and prolonged mitosis progression | Homo sapiens | |
| BI 2536 | inhibition via binding in the ATP-binding site | Homo sapiens | |
| FDPPLHSpTA | a PBIP1-derived phosphopeptide, the N-terminal phenylalanine sits in the hydrophobic pocket | Homo sapiens | |
| GSK461364A | inhibition via binding in the ATP-binding site | Homo sapiens | |
| MAGPMQSpTPLNGAKK | the peptide inhibitor blocks the interaction between the Plk1 PBD and Cdc25C | Homo sapiens | |
| additional information | the polo-box domain is unique to the five-member family of polo-like kinases, and its inhibition is sufficient to inhibit the enzyme. Small molecule and peptide-based inhibitors of the Plk1 polo-box domain, PBD, detailed overview | Homo sapiens | |
| N-(26-(4-[(4-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino]-3-methoxybenzoyl)amino]piperidin-1-yl)-19-oxo-3,6,9,12,15-pentaoxa-18-azahexacosan-1-oyl)glycyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-alaninamide | - |
Homo sapiens | |
| N-(3-(2-[(8-[4-[(4-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino]-3-methoxybenzoyl)amino]piperidin-1-yl]octanoyl)amino]ethoxy)propanoyl)glycyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-alaninamide | - |
Homo sapiens | |
| N-(48-(4-[(4-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino]-3-methoxybenzoyl)amino]piperidin-1-yl)-41-oxo-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azaoctatetracontan-1-oyl)glycyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-alaninamide | - |
Homo sapiens | |
| N-(72-(4-[(4-[[(7S)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino]-3-methoxybenzoyl)amino]piperidin-1-yl)-65-oxo-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46,49,52,55,58,61-icosaoxa-64-azadoheptacontan-1-oyl)glycyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-alaninamide | - |
Homo sapiens | |
| N-acetyl-N-(6-phenylhexyl)glycyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threoninamide | - |
Homo sapiens | |
| N-adamantylacetyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-methioninamide | i.e PL-55, PLHSpT-based peptide | Homo sapiens | |
| N-[3-(1-benzothiophen-2-yl)propanoyl]-alpha-aspartyl-L-prolyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-alaninamide | - |
Homo sapiens | |
| NMS-P937 | inhibition via binding in the ATP-binding site | Homo sapiens | |
| PL-42 | (MeO)3PhCH2PLHSpTM | Homo sapiens | |
| PL-49 | cyclohexylmethyl-PLHSpTM | Homo sapiens | |
| Volasertib | BI6727, inhibition via binding in the ATP-binding site | Homo sapiens | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + Cdc25C | Homo sapiens | the protein phosphatase is directly phosphorylated by Plk1 | ADP + phosphorylated Cdc25C | - |
? | |
| ATP + PBIP1 | Homo sapiens | phosphorylation on Thr78 by Plk1 | ADP + phosphorylated PBIP1 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q9NYY3 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + Cdc25C | the protein phosphatase is directly phosphorylated by Plk1 | Homo sapiens | ADP + phosphorylated Cdc25C | - |
? | |
| ATP + PBIP1 | phosphorylation on Thr78 by Plk1 | Homo sapiens | ADP + phosphorylated PBIP1 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Plk1 | - |
Homo sapiens |
| Polo-like kinase 1 | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.0000025 | 0.000017 | pH and temperature not specified in the publication | Homo sapiens | 1-acetyl-L-prolyl-L-leucyl-3-(8-phenyloctyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide | |
| 0.000014 | - |
pH and temperature not specified in the publication | Homo sapiens | (4R)-1-acetyl-4-(4-phenylbutoxy)prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threoninamide | |
| 0.00025 | - |
pH and temperature not specified in the publication | Homo sapiens | N-[3-(1-benzothiophen-2-yl)propanoyl]-alpha-aspartyl-L-prolyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-alaninamide | |
| 0.00036 | - |
pH and temperature not specified in the publication | Homo sapiens | PL-49 | |
| 0.00082 | - |
pH and temperature not specified in the publication | Homo sapiens | N-adamantylacetyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threonyl-L-methioninamide | |
| 0.00108 | - |
pH and temperature not specified in the publication | Homo sapiens | (1R)-1-[(3S,6S,9S,12S,15S)-19-(6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl)-3-carbamoyl-9-(hydroxymethyl)-15-(2-methylpropyl)-5,8,11,14,17,20-hexaoxo-12-[[1-(9-phenylnonyl)-1H-imidazol-5-yl]methyl]-1-thia-4,7,10,13,16,19-hexaazacyclohenicosan-6-yl]ethyl phosphate | |
| 0.00114 | - |
pH and temperature not specified in the publication | Homo sapiens | (4E)-5-methyl-4-[[(2-methylbenzoyl)oxy]imino]-2-(propan-2-yl)cyclohexa-2,5-dien-1-one | |
| 0.00136 | - |
pH and temperature not specified in the publication | Homo sapiens | (4E)-5-methyl-4-[[(2-methylbenzoyl)oxy]imino]-2-(propan-2-yl)cyclohexa-2,5-dien-1-one | |
| 0.0018 | - |
pH and temperature not specified in the publication | Homo sapiens | PL-42 | |
| 0.00256 | - |
pH and temperature not specified in the publication | Homo sapiens | (1R)-1-[(3S,6S,9S,12S,15S)-19-(6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl)-3-carbamoyl-9-(hydroxymethyl)-12-(1H-imidazol-5-ylmethyl)-15-(2-methylpropyl)-5,8,11,14,17,20-hexaoxo-1-thia-4,7,10,13,16,19-hexaazacyclohenicosan-6-yl]ethyl phosphate | |
| 0.0032 | - |
pH and temperature not specified in the publication | Homo sapiens | (2Z)-2-(5-bromo-2-methoxybenzylidene)-6-methyl-7H-[1,3]thiazolo[3,2-b][1,2,4]triazine-3,7(2H)-dione | |
| 0.0045 | - |
pH and temperature not specified in the publication | Homo sapiens | (3S)-4-amino-4-oxo-3-([[2-(4-phenylbutyl)-1-(2-phenylethyl)-1H-benzimidazol-5-yl]carbonyl]amino)butan-2-yl phosphate | |
| 0.055 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-acetyl-L-prolyl-L-leucyl-3-[3-(2-hydroxyethyl)-1-(8-phenyloctyl)-1H-imidazol-3-ium-5-yl]-L-alanyl-L-seryl-O-[[[(2,2-dimethylpropanoyl)oxy]methoxy](hydroxy)phosphoryl]-L-threoninamide | |
| 0.085 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-acetyl-L-prolyl-L-leucyl-3-[3-(2-hydroxyethyl)-1-(8-phenyloctyl)-1H-imidazol-3-ium-5-yl]-L-alanyl-L-seryl-O-phosphono-L-threoninamide | |
| 0.38 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-(26-oxo-2,5,8,11,14,17,20,23-octaoxahexacosan-26-yl)-L-prolyl-L-leucyl-3-(8-phenyloctyl)-L-histidyl-L-seryl-(3R)-4-phosphono-L-valinamide | |
| 122 | - |
pH and temperature not specified in the publication | Homo sapiens | (4R)-1-acetyl-4-[[(E)-(3-phenylpropylidene)amino]oxy]prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threoninamide | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the polo-box domain, PBD, is unique to the five-member family of polo-like kinases, found in only Plk1, Plk2, Plk3 and Plk5. Plk4 does not have a PBD, as it has only a single polo box. Unlike the other family members, Plk5 does not contain a kinase domain | Homo sapiens |
| additional information | in Plk1, the phosphopeptide binds to a shallow cleft formed between polo box 1 (PB1) and polo box 2 (PB2), which are clamped together by the Polo-cap | Homo sapiens |
| physiological function | the Plk1 polo-box domain is involved in substrate binding and in determining the correct subcellular localization of Plk1, with phospho-dependent substrate recognition by the PBD being necessary for proper mitotic progression. Binding of Plk1 to PBIP1 mediates centromeric localization of Plk1 and is important for chromosome segregation | Homo sapiens |
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