PDBsum entry 4xo7

Oxidoreductase

PDB id: 4xo7

Contents

Protein chains

322 a.a.

Ligands

NAP ×2

ASD ×2

SO4 ×2

Waters ×335

PDB id:

4xo7

Name:

Oxidoreductase

Title:

Crystal structure of human 3-alpha hydroxysteroid dehydrogenase type 3 in complex with NADP+, 5alpha-androstan-3,17-dione and (3beta, 5alpha)-3-hydroxyandrostan-17-one

Structure:

Aldo-keto reductase family 1 member c2. Chain: a, b. Synonym: 3-alpha-hsd3,chlordecone reductase homolog hakrd,dihydrodiol dehydrogenase 2,dd2,dihydrodiol dehydrogenase/bile acid-binding protein,dd/babp,trans-1,2-dihydrobenzene-1,2-diol dehydrogenase,type iii 3-alpha-hydroxysteroid dehydrogenase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: akr1c2, ddh2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.75Å R-factor: 0.164 R-free: 0.205

Authors:

B.Zhang,X.-J.Hu,S.-X.Lin

Key ref:

B.Zhang et al. (2016). Human 3α-hydroxysteroid dehydrogenase type 3: structural clues of 5α-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth. Biochem J, 473, 1037-1046. PubMed id: 26929402 DOI: 10.1042/BCJ20160083

Date:

16-Jan-15 Release date: 17-Feb-16

Protein chains

P52895  (AK1C2_HUMAN) -  Aldo-keto reductase family 1 member C2 from Homo sapiens

Seq: 323 a.a.

Struc: 322 a.a.

Enzyme reactions

• Enzyme class 1: E.C.1.-.-.-
• Enzyme class 2: E.C.1.1.1.112 - indanol dehydrogenase.
• Reaction:
  1. (S)-indan-1-ol + NAD⁺ = indan-1-one + NADH + H⁺
  2. (S)-indan-1-ol + NADP⁺ = indan-1-one + NADPH + H⁺

(S)-indan-1-ol + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = indan-1-one + NADH + H(+)

(S)-indan-1-ol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = indan-1-one + NADPH + H(+)

• Enzyme class 3: E.C.1.1.1.209 - 3(or 17)alpha-hydroxysteroid dehydrogenase.
• Reaction:
  1. androsterone + NADP⁺ = 5alpha-androstan-3,17-dione + NADPH + H⁺
  2. androsterone + NAD⁺ = 5alpha-androstan-3,17-dione + NADH + H⁺

androsterone (Bound ligand (Het Group name = ASD) corresponds exactly) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 5alpha-androstan-3,17-dione + NADPH + H(+)

androsterone (Bound ligand (Het Group name = ASD) corresponds exactly) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 5alpha-androstan-3,17-dione + NADH + H(+)

• Enzyme class 4: E.C.1.1.1.357 - 3alpha-hydroxysteroid 3-dehydrogenase.
• Reaction:
  1. a 3alpha-hydroxysteroid + NADP⁺ = a 3-oxosteroid + NADPH + H⁺
  2. a 3alpha-hydroxysteroid + NAD⁺ = a 3-oxosteroid + NADH + H⁺

3alpha-hydroxysteroid (Bound ligand (Het Group name = ASD) matches with 86.36% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 3-oxosteroid + NADPH + H(+)

3alpha-hydroxysteroid (Bound ligand (Het Group name = ASD) matches with 86.36% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 3-oxosteroid + NADH + H(+)

• Enzyme class 5: E.C.1.1.1.53 - 3alpha(or 20beta)-hydroxysteroid dehydrogenase.
• Reaction: androstan-3alpha,17beta-diol + NAD⁺ = 17beta-hydroxyandrostanone + NADH + H⁺

androstan-3alpha,17beta-diol (Bound ligand (Het Group name = ASD) corresponds exactly) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 17beta-hydroxyandrostanone + NADH + H(+)

• Enzyme class 6: E.C.1.1.1.62 - 17beta-estradiol 17-dehydrogenase.
• Reaction:
  1. 17beta-estradiol + NAD⁺ = estrone + NADH + H⁺
  2. 17beta-estradiol + NADP⁺ = estrone + NADPH + H⁺

17beta-estradiol + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = estrone (Bound ligand (Het Group name = ASD) matches with 95.24% similarity) + NADH + H(+)

17beta-estradiol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = estrone (Bound ligand (Het Group name = ASD) matches with 95.24% similarity) + NADPH + H(+)

• Enzyme class 7: E.C.1.3.1.20 - trans-1,2-dihydrobenzene-1,2-diol dehydrogenase.
• Reaction:
  1. (1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP⁺ = catechol + NADPH + H⁺
  2. (1S,2S)-1,2-dihydrobenzene-1,2-diol + NADP⁺ = catechol + NADPH + H⁺

(1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = catechol + NADPH + H(+)

(1S,2S)-1,2-dihydrobenzene-1,2-diol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = catechol + NADPH + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1042/BCJ20160083

Biochem J 473:1037-1046 (2016)

PubMed id: 26929402

Human 3α-hydroxysteroid dehydrogenase type 3: structural clues of 5α-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth.

B.Zhang, X.J.Hu, X.Q.Wang, J.F.Thériault, D.W.Zhu, P.Shang, F.Labrie, S.X.Lin.

ABSTRACT

No abstract given.