Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3alpha-hydroxysteroid/dihydrodiol dehydrogenase

Bennett, M.J.; Albert, R.H.; Jez, J.M.; Ma, H.; Penning, T.M.; Lewis, M.; Structure 5, 799-812 (1997)

 show all sequences of 1.3.1.20

Data extracted from this reference:

Cloned(Commentary)
Commentary Organism
overexpression in Escherichia coli Rattus norvegicus
Crystallization (Commentary)
Crystallization Organism
complexed with NADP+ and testosterone, 10fold molar excess of NADP+, 'waterbug' dialysis method in 10 mM potassium phosphate buffer, pH 7.0, containing 1 mM EDTA, 1 mM 2-mrcapthoethanol, 5% acetonitrile and 0.2 mM testosterone, and crystallization in presence of polethylene glycol 8000 in hanging drops at room temperature, single crystals; cryocrystallization: crystals were soaked in 21% polyethylene glycol 8000, 0.1 M sodium cacodylate, pH 6.4, 1.25 mM NADP+, 0.1 mM testosterone and 15% 2-methyl-2,4-pentanediol as cryoprotectant; structure determination, cofactor and substrate binding site, and model building Rattus norvegicus
Natural Substrates/ Products (Substrates)
Natural Substrates Organism Commentary (Nat. Sub.) Natural Products Commentary (Nat. Pro.) Organism (Nat. Pro.) Reversibility
5alpha-dihydrotestosterone + NADPH Rattus norvegicus
-
 5alpha-androstan-3alpha,17beta-diol + NADP+
-
 Rattus norvegicus r
Organism
Organism Primary Accession No. (UniProt) Commentary Textmining
Rattus norvegicus
-
-
-
Reaction
Reaction Commentary Organism
trans-1,2-dihydrobenzene-1,2-diol + NADP+ = catechol + NADPH + H+ cofactor binding and catalytic triad, alpha/beta-barrel structure; enzyme termed 3alpha-hydroxysteroid/dihydrodiol dehydrogenase, structure-based catalytic mechanism analysis, ordered bi-bi mechanism; structure analysis reveals that the enzyme belongs to the aldo-keto reductase superfamily, like 3alpha-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, 20alpha-hydroxysteroid dehydrogenase, aldose reductase, and aldehyde reductase; termed AKR1C as member of the aldo-keto-superfamily, overview Rattus norvegicus
Source Tissue
Source Tissue Commentary Organism Textmining
liver
-
 Rattus norvegicus
-
Substrates and Products (Substrate)
Substrates Commentary Substrates Literature (Substrates) Organism Products Commentary (Products) Literature (Products) Organism (Products) Reversibility
3-keto steroid + NAD(P)H
-
 349263 Rattus norvegicus 3alpha-hydroxy steroid + NAD(P)+
-
 349263 Rattus norvegicus r
5alpha-dihydrotestosterone + NADPH
-
 349263 Rattus norvegicus 5alpha-androstan-3alpha,17beta-diol + NADP+
-
 349263 Rattus norvegicus r
Subunits
Subunits Commentary Organism
monomer 1 * 37029, sequence determination Rattus norvegicus
Cofactor
Cofactor Commentary Organism Structure
NADP+
-
 Rattus norvegicus
NADPH
-
 Rattus norvegicus
Cloned(Commentary) (protein specific)
Commentary Organism
overexpression in Escherichia coli Rattus norvegicus
Cofactor (protein specific)
Cofactor Commentary Organism Structure
NADP+
-
 Rattus norvegicus
NADPH
-
 Rattus norvegicus
Crystallization (Commentary) (protein specific)
Crystallization Organism
complexed with NADP+ and testosterone, 10fold molar excess of NADP+, 'waterbug' dialysis method in 10 mM potassium phosphate buffer, pH 7.0, containing 1 mM EDTA, 1 mM 2-mrcapthoethanol, 5% acetonitrile and 0.2 mM testosterone, and crystallization in presence of polethylene glycol 8000 in hanging drops at room temperature, single crystals; cryocrystallization: crystals were soaked in 21% polyethylene glycol 8000, 0.1 M sodium cacodylate, pH 6.4, 1.25 mM NADP+, 0.1 mM testosterone and 15% 2-methyl-2,4-pentanediol as cryoprotectant; structure determination, cofactor and substrate binding site, and model building Rattus norvegicus
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates Organism Commentary (Nat. Sub.) Natural Products Commentary (Nat. Pro.) Organism (Nat. Pro.) Reversibility
5alpha-dihydrotestosterone + NADPH Rattus norvegicus
-
 5alpha-androstan-3alpha,17beta-diol + NADP+
-
 Rattus norvegicus r
Source Tissue (protein specific)
Source Tissue Commentary Organism Textmining
liver
-
 Rattus norvegicus
-
Substrates and Products (Substrate) (protein specific)
Substrates Commentary Substrates Literature (Substrates) Organism Products Commentary (Products) Literature (Products) Organism (Products) Reversibility
3-keto steroid + NAD(P)H
-
 349263 Rattus norvegicus 3alpha-hydroxy steroid + NAD(P)+
-
 349263 Rattus norvegicus r
5alpha-dihydrotestosterone + NADPH
-
 349263 Rattus norvegicus 5alpha-androstan-3alpha,17beta-diol + NADP+
-
 349263 Rattus norvegicus r
Subunits (protein specific)
Subunits Commentary Organism
monomer 1 * 37029, sequence determination Rattus norvegicus

See also following references to EC number 1.3.1.20 (sorted by year of publication):
No.1st authorPub
Med		titleorganimsjournalvolumepagesyearActivating CompoundApplicationCloned(Commentary)Crystallization (Commentary)EngineeringGeneral StabilityInhibitorsKM Value [mM]LocalizationMetals/IonsMolecular Weight [Da]Natural Substrates/ Products (Substrates)Organic Solvent StabilityOrganismOxidation StabilityPosttranslational ModificationPurification (Commentary)ReactionRenatured (Commentary)Source TissueSpecific Activity [micromol/min/mg]Storage StabilitySubstrates and Products (Substrate)SubunitsTemperature Optimum [°C]Temperature Range [°C]Temperature Stability [°C]Turnover Number [1/s]pH OptimumpH RangepH StabilityCofactorKi Value [mM]pI ValueIC50 ValueActivating Compound (protein specific)Application (protein specific)Cloned(Commentary) (protein specific)Cofactor (protein specific)Crystallization (Commentary) (protein specific)Engineering (protein specific)General Stability (protein specific)IC50 Value (protein specific)Inhibitors (protein specific)Ki Value [mM] (protein specific)KM Value [mM] (protein specific)Localization (protein specific)Metals/Ions (protein specific)Molecular Weight [Da] (protein specific)Natural Substrates/ Products (Substrates) (protein specific)Organic Solvent Stability (protein specific)Oxidation Stability (protein specific)Posttranslational Modification (protein specific)Purification (Commentary) (protein specific)Renatured (Commentary) (protein specific)Source Tissue (protein specific)Specific Activity [micromol/min/mg] (protein specific)Storage Stability (protein specific)Substrates and Products (Substrate) (protein specific)Subunits (protein specific)Temperature Optimum [°C] (protein specific)Temperature Range [°C] (protein specific)Temperature Stability [°C] (protein specific)Turnover Number [1/s] (protein specific)pH Optimum (protein specific)pH Range (protein specific)pH Stability (protein specific)pI Value (protein specific)ExpressionGeneral InformationGeneral Information (protein specific)Expression (protein specific)KCat/KM [mM/s]KCat/KM [mM/s] (protein specific)
697571ChangOverexpression of dihydrodiol ...Homo sapiensDigest.Dis.Sci.54342-3472009-1------1--1-1-----21-1-------------1---------1--1-----21-1---------------
684150CarboneStructure of monkey dimeric di ...Macaca fascicularis, Macaca fuscataActa Crystallogr. Sect. D64532-5422008--2230-426---2-2--2-----42---10---3--23--23230-234-26---2---2----42---10----------
686023CarboneStructural and functional feat ...Bos taurus, Macaca fascicularis, Mus musculus, Pongo abelii, Sus scrofaCell. Mol. Life Sci.651464-14742008---15-8--2---5-----3--152-------10--2---1015-28---2-------3--152--------------
701119CarboneStructures of dimeric dihydrod ...Macaca fascicularisProteins Struct.Funct.Genet.70176-1872008--113-1---11-1--1---3-12--1-1--2--1--1213-11----11---1--3-12--1-1---------
685913PanDihydrodiol dehydrogenase in d ...Homo sapiensCancer Chemother. Pharmacol.59697-7022007-------------1-----2--1--------1------1----------------2--1---------------
687141WangReversal of inflammation-assoc ...Homo sapiensInt. J. Cancer1202019-202720071-----3---1--2-----1--1--------1---2--2----6----2------2--2---------------
689972Carbone-Structures of dimeric dihydrod ...Macaca fascicularisProteins Struct. Funct. Bioinform.70176-1872007--113-1------1--1-----21--1----1--1--1113-11---------1----21--1-----------
671358Hung-Expression of dihydrodiol dehy ...Homo sapiensAnticancer Res.262949-29562006-1--1--------1-----6----------------1---1--------------6------------------
673371ChengA possible role for dihydrodio ...Homo sapiensEnviron. Mol. Mut.4814-212006-1--1--------1-----3----------------1---1--------------3------------------
675089ChowExpression of dihydrodiol dehy ...Homo sapiensJ. Dermatol. Sci.41205-2122006-1-----------1-----1----------------1------------------1------------------
673903ChenOverexpression of dihydrodiol ...Homo sapiensGynecol. Oncol.97110-1172005-1-----------1-----1----------------1------------------1------------------
655159DengUbiquitous induction of resist ...Homo sapiensCancer Chemother. Pharmacol.54301-3072004------7------1-----15-1--------1------1----7-----------15-1---------------
655236SeikeOxidative DNA damage induced b ...Mus musculusChem. Res. Toxicol.171445-14512004-1---------1-1--------1-------------1------------1--------1---------------
655744WangInverse expression of dihydrod ...Homo sapiensInt. J. Cancer111246-2512004-1-----------1----------------------1-------------------------------------
657392TangHydroxychavicol modulates benz ...Homo sapiensToxicol. Lett.152235-2432004-----------1-1-----1--1--------------------------1-----1--1---------------
656885YangReduction of dihydrodiol dehyd ...Homo sapiensOncol. Rep.10271-2762003-1-----------1-----1----------------1------------------1------------------
349258El-KabbaniCrystallization and preliminar ...Macaca fuscataActa Crystallogr. Sect. D58163-1642002--11---------1--11-1--11-------1-----111-------------1-1--11--------------
655321HigakiMolecular characterization of ...Macaca fascicularis, Macaca fuscata fuscataDrug Metab. Pharmacokinet.17348-3562002-------10-----4-----22-1922--102--1------1------10---------22-1922--102---------
656043DengIncreased expression of dihydr ...Homo sapiensJ. Biol. Chem.27715035-150432002----1-2------1-----29-3--------1------1-1--2-----------29-3---------------
286128AokiIdentity of dimeric dihydrodio ...Canis sp., Homo sapiens, Macaca fuscata, Oryctolagus cuniculus, Sus scrofaChem. Biol. Interact.130-132775-7842001------910-----9--31-279-29-5------10------10----9-10-------3-279-29-5-------------
349250TeradaSite-directed mutagenesis stud ...Bos taurusChem. Biol. Interact.130-132833-8452001--1-7-3----1-1--11-11-3-----4--2-----12-7--3-----1---1-11-3-----4---------
286127AsadaRoles of His-79 and Tyr-180 of ...Macaca fuscataBiochem. Biophys. Res. Commun.278333-3372000--1-3-212--1--1--11-1--31-------2-----12-3--2-12--1----1-1--31--------------
349252KumeCharacterization of a novel va ...Homo sapiensPharmacogenetics9763-77119991-1-3-7---11-1--11-12-1311--8---1---1-11-3--7----11---1-12-1311--8----------
349260BurczynskiExpression and characterizatio ...Homo sapiensBiochemistry376781-67901998--1----12-----1--11-14-6----14---1-----11------12-------1-14-6----14----------
349261MatsuuraRoles of the C-terminal domain ...Homo sapiensBiochem. J.336429-43619984-1-8-7------3--1--2--1--------1---4-11-8--7---------1-2--1---------------
349262MatsuuraIdentification of amino acid r ...Homo sapiensBiochem. J.32361-641997-------------1-----1-----------------------------------1------------------
349263BennettSteroid recognition and regula ...Rattus norvegicusStructure5799-8121997--11-------1-1---1-1--21-------2-----121---------1-----1--21--------------
349259HaraRelationship of human liver di ...Homo sapiensBiochem. J.313373-3761996--1---9------1--1--11-5----6---2-----12----9---------1-11-5----6----------
349253MiyabeKinetic studies of the inhibit ...Homo sapiensBiol. Pharm. Bull.189-121995------8----1-1-----1--3--------27-----2----87----1-----1--3---------------
349255DeyashikiExpression and kinetic propert ...Homo sapiensJ. Biochem.118285-2901995--1---13---2--1-----11-151-------12----11----132---2------11-151--------------
349256NanjoEnzymic characterization of a ...Bos taurusBiochim. Biophys. Acta124453-611995------1141----1--1--1--11----14---2------2----1-141------1-1--11----14----------
349254SatoPurification and characterizat ...Canis sp.J. Biochem.116711-7171994------8---1--1--1--91-241-------2------2----8----1----1-91-241--------------
349257HoogThree-dimensional structure of ...Rattus norvegicusProc. Natl. Acad. Sci. USA912517-25211994-1-13-1----1-1---1-1--31-------2----1-213--1-----1-----1--31--------------
349251NanjoUnique dihydrodiol specific de ...Bos taurusAdv. Exp. Med. Biol.328371-3771993------54-----1--11-1--6-1------14-----1----544-------1-1--6-1-------------
349237NakagawaDimeric dihydrodiol dehydrogen ...Macaca fascicularis, Macaca fuscataJ. Biochem.1061104-11091989-------9--13-2--1--22-1412--92--3------3------9--13---1-22-1412--92---------
349238PenningNon-K-region o-quinones as enz ...Rattus norvegicusBiochemistry284505-45111989------2-1--1-1-----11-1--------------------2--1--1-----11-1---------------
349239NakagawaIdentification of two dihydrod ...Mus musculusBiochem. J.106633-6381989------971--4-1--11-6--1611-2----3------3----9-71--4---1-6--1611-2-----------
349240HaraIsolation from pig lens of two ...Sus scrofaBiochem. J.264403-40719893-----12----2-1--11-4--721---4--4---3--4----12-----2---1-4--721---4---------
349241SmithgallSpectroscopic identification o ...Rattus norvegicusJ. Biol. Chem.2631814-18201988--------1--3-1-----1--4--------1------1-------1--3-----1--4---------------
349242HaraPurification and partial chara ...Macaca fuscataBiochem. Biophys. Res. Commun.1451260-12661987-------6--11-1--1--22-111----1--2------2------6--11---1-22-111----1---------
349243MatsuuraPurification and properties of ...Cavia porcellusBiochim. Biophys. Acta912270-27719873-----8-1-11-2--11-31-181-------2---3--2----8--1-11---1-31-181--------------
349244SmithgallRegio- and stereospecificity o ...Rattus norvegicusJ. Biol. Chem.2616184-61911986--------3--2-4---1-3--7--------2------2-------3--2-----3--7---------------
349245BoutinRat liver microsomal 3alpha-hy ...Rattus norvegicusBiochem. Biophys. Res. Commun.135795-8011986------1-3--1-2--11-21-2--------1------1----1--3--1---1-21-2---------------
349246BolcsakPurification of mouse liver be ...Mus musculusJ. Biol. Chem.2587252-72551983-------1--41-1--1---1-51----3--2------2------1--41---1--1-51----3---------
349247VogelRat liver cytoplasmic dihydrod ...Rattus norvegicusJ. Biol. Chem.2559621-96251980-------11-11-1--1--11-41-------2------2------11-11---1-11-41--------------