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CATH domain | Related DB codes (homologues) |
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3.40.50.720 : Rossmann fold | S00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109 |
Enzyme Name | UniProtKB | KEGG |
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| P19992 |
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Protein name | 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase | 3alpha(or 20beta)-hydroxysteroid dehydrogenasecortisone reductase(R)-20-hydroxysteroid dehydrogenasedehydrogenase, 20beta-hydroxy steroidDelta4-3-ketosteroid hydrogenase20beta-hydroxysteroid dehydrogenase3alpha,20beta-hydroxysteroid:NAD+-oxidoreductaseNADH-20beta-hydroxysteroid dehydrogenase20beta-HSD |
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Synonyms | EC 1.1.1.53 |
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Pfam | PF00106 (adh_short) [Graphical view]
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KEGG pathways | MAP code | Pathways |
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MAP00120 | Bile acid biosynthesis | MAP00140 | C21-Steroid hormone metabolism |
UniProtKB:Accession Number | P19992 |
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Entry name | HSD_STREX |
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Activity | Androstan-3-alpha,17-beta-diol + NAD(+) = 17-beta-hydroxyandrostan-3-one + NADH. |
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Subunit | Homotetramer. |
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Subcellular location |
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Cofactor |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[12] |
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| [13] | Fig.8b, p.632-637 |
| [15] | Fig.3 |
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references | [1] |
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PubMed ID | 168869 |
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Journal | Biochem J |
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Year | 1975 |
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Volume | 145 |
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Pages | 483-9 |
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Authors | Gibb W, Jeffery J |
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Title | The altered specificity of cortisone reductase with certain retroandrostan-3-one substrates. |
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[2] |
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PubMed ID | 172381 |
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Journal | Biochem Soc Trans |
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Year | 1975 |
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Volume | 3 |
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Pages | 674-5 |
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Authors | White IH, Jeffery J |
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Title | The functioning of a nicotinamide--adenine dinucleotide-dependent dehydrogenase and the structure adjacent to the reacting carbon atom of the substrate. |
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[3] |
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PubMed ID | 902901 |
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Journal | Biochem Soc Trans |
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Year | 1977 |
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Volume | 5 |
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Pages | 723-4 |
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Authors | White IH, Jeffery J |
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Title | Cortisone reductase and some small non-steroid analogues of its steroid substrates. |
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[4] |
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PubMed ID | 6938245 |
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Journal | Biochim Biophys Acta |
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Year | 1980 |
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Volume | 616 |
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Pages | 143-52 |
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Authors | Pasta P, Carrea G, Longhi R, Antonini E |
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Title | Renaturation and urea-induced denaturation of 20 beta-hydroxysteroid dehydrogenase studied in solution and in the immobilized state. |
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[5] |
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PubMed ID | 6930328 |
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Journal | Chem Pharm Bull (Tokyo) |
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Year | 1980 |
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Volume | 28 |
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Pages | 730-6 |
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Authors | Hayakawa T, Tanimoto T, Kawamura J |
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Title | Structural requirements in 20-oxo-steroids for interaction with the catalytic site of 20 beta-hydroxysteroid dehydrogenase. |
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[6] |
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PubMed ID | 6929616 |
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Journal | Steroids |
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Year | 1980 |
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Volume | 35 |
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Pages | 111-8 |
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Authors | Sweet F, Ahmed R, Morgan TE, Sweet BC |
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Title | Bifunctional enzyme activity at the same active site: competitive inhibition kinetics with 3 alpha/20 beta-hydroxysteroid dehydrogenase. |
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[7] |
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PubMed ID | 6944159 |
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Journal | Chem Pharm Bull (Tokyo) |
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Year | 1981 |
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Volume | 29 |
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Pages | 476-84 |
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Authors | Kawamura J, Tanimoto T, Fukuda H, Hayakawa T |
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Title | Structural requirements in 20-oxo-steroids for interaction with the binding site of 20beta-hydroxysteroid dehydrogenase. |
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[8] |
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PubMed ID | 6587118 |
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Journal | J Mol Biol |
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Year | 1984 |
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Volume | 175 |
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Pages | 225-7 |
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Authors | Fitzgerald PM, Duax WL, Punzi JS, Orr JC |
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Title | Crystallization and preliminary crystallographic study of 3 alpha, 20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans. |
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[9] |
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PubMed ID | 3455925 |
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Journal | J Biol Chem |
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Year | 1986 |
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Volume | 261 |
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Pages | 1306-8 |
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Authors | Ghosh D, Punzi JS, Duax WL |
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Title | Crystals of active tetramers of 3 alpha, 20 beta-hydroxysteroid dehydrogenase. |
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[10] |
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PubMed ID | 2064995 |
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Journal | J Steroid Biochem Mol Biol |
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Year | 1991 |
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Volume | 38 |
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Pages | 787-94 |
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Authors | Ohno S, Nakajin S, Shinoda M |
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Title | 20 beta-hydroxysteroid dehydrogenase of neonatal pig testis: 3 alpha/beta-hydroxysteroid dehydrogenase activities catalyzed by highly purified enzyme. |
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[11] |
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Comments | X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) |
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Medline ID | 92052211 |
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PubMed ID | 1946424 |
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Journal | Proc Natl Acad Sci U S A |
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Year | 1991 |
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Volume | 88 |
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Pages | 10064-8 |
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Authors | Ghosh D, Weeks CM, Grochulski P, Duax WL, Erman M, Rimsay RL, Orr JC |
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Title | Three-dimensional structure of holo 3 alpha,20 beta-hydroxysteroid dehydrogenase: a member of a short-chain dehydrogenase family. |
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Related UniProtKB | P19992 |
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[12] |
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Comments | X-ray crystallography |
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PubMed ID | 7866748 |
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Journal | Structure |
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Year | 1994 |
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Volume | 2 |
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Pages | 973-80 |
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Authors | Ghosh D, Erman M, Wawrzak Z, Duax WL, Pangborn W |
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Title | Mechanism of inhibition of 3 alpha, 20 beta-hydroxysteroid dehydrogenase by a licorice-derived steroidal inhibitor. |
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Related PDB | 1hdc |
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[13] |
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Comments | X-ray crystallography |
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PubMed ID | 7922040 |
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Journal | Structure |
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Year | 1994 |
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Volume | 2 |
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Pages | 629-40 |
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Authors | Ghosh D, Wawrzak Z, Weeks CM, Duax WL, Erman M |
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Title | The refined three-dimensional structure of 3 alpha,20 beta-hydroxysteroid dehydrogenase and possible roles of the residues conserved in short-chain dehydrogenases. |
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Related PDB | 2hsd |
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[14] |
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PubMed ID | 7696141 |
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Journal | J Steroid Biochem Mol Biol |
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Year | 1995 |
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Volume | 52 |
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Pages | 209-18 |
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Authors | Buczko E, Koh YC, Miyagawa Y, Dufau ML |
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Title | The rat 17 alpha-hydroxylase-17,20-desmolase (CYP17) active site: computerized homology modeling and site directed mutagenesis. |
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[15] |
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PubMed ID | 9029722 |
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Journal | Steroids |
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Year | 1997 |
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Volume | 62 |
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Pages | 95-100 |
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Authors | Duax WL, Ghosh D |
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Title | Structure and function of steroid dehydrogenases involved in hypertension, fertility, and cancer. |
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comments | This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, along with Drosophia alcohol dehydrogenase (S00319 in EzCatDB). This enzyme has got a catalytic triad composed of conserved residues, Ser, Tyr, and Lys. The conformation of these residues, compared to that of the NAD molecule, seems to be similar to that of the homologous enzymes. Thus, the catalytic site seems to catalyze the following reversible reactions. (A) Hydride transfer from substrate to NAD (Dehydrogenation): (A0) Lys156 modulates the activity (or pKa) of Tyr152 via 2'-hydroxyl group of NAD, along with the N1 atom of the nicotinamide group in NAD, whereas Ser139 modulates the pKa of hydroxyl oxygen of the substrate. (A1) Tyr152 acts as a general base to deprotonate the hydroxyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the carbon atom with the hydroxyl group of the substrate to the C4 atom of the nicotinamide. (B) Hydride transfer from NADH to substrate (Reduction): (B0) Lys156 modulates the activity (or pKa) of Tyr152 via 2'-hydroxyl group of NAD(P)H, along with the N1 atom of the nicotinamide group in NADH, whereas Ser139 modulates the pKa of carbonyl oxygen of the substrate. (B1) Tyr152 acts as a general acid to protonate the carbonyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4 atom of the nicotinamide to the carbonyl carbon of the substrate.
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created | updated |
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2004-07-13 | 2011-06-21 |
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