PDBsum entry 4dbs

Oxidoreductase/oxidoreductase inhibitor

PDB id: 4dbs

Contents

Protein chain

315 a.a.

Ligands

NAP ×2

0HV ×4

Waters ×442

PDB id:

4dbs

Name:

Oxidoreductase/oxidoreductase inhibitor

Title:

Crystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 (akr1c3) in complex with NADP+ and 3'-[(4-nitronaphthalen-1-yl) amino]benzoic acid

Structure:

Aldo-keto reductase family 1 member c3. Chain: a, b. Synonym: 17-beta-hydroxysteroid dehydrogenase type 5, 17-beta-hsd 5, 3-alpha-hsd type ii, 3-alpha-hydroxysteroid dehydrogenase type 2, 3- alpha-hsd type 2, chlordecone reductase homolog hakrb, dihydrodiol dehydrogenase 3, dd-3, dd3, dihydrodiol dehydrogenase type i, ha1753, indanol dehydrogenase, prostaglandin f synthase, pgfs, testosterone 17-beta-dehydrogenase 5, trans-1,2-dihydrobenzene-1,2-diol dehydrogenase.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: akr1c3, ddh1, hsd17b5, kiaa0119, pgfs. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.85Å R-factor: 0.183 R-free: 0.222

Authors:

M.Chen,D.W.Christianson,J.D.Winkler,T.M.Penning

Key ref:

M.Chen et al. (2012). Crystal structures of AKR1C3 containing an N-(aryl)amino-benzoate inhibitor and a bifunctional AKR1C3 inhibitor and androgen receptor antagonist. Therapeutic leads for castrate resistant prostate cancer. Bioorg Med Chem Lett, 22, 3492-3497. PubMed id: 22507964

Date:

16-Jan-12 Release date: 28-Mar-12

Protein chains

P42330  (AK1C3_HUMAN) -  Aldo-keto reductase family 1 member C3 from Homo sapiens

Seq: 323 a.a.

Struc: 315 a.a.

Enzyme reactions

• Enzyme class 1: E.C.1.1.1.188 - prostaglandin-F synthase.
• Reaction: prostaglandin F2alpha + NADP⁺ = prostaglandin D2 + NADPH + H⁺

prostaglandin F2alpha (Bound ligand (Het Group name = NAP) corresponds exactly) + NADP(+) = prostaglandin D2 + NADPH + H(+)

• Enzyme class 2: E.C.1.1.1.210 - 3beta-(or 20alpha)-hydroxysteroid dehydrogenase.
• Reaction: 5alpha-androstane-3beta,17beta-diol + NADP⁺ = 17beta-hydroxy-5alpha- androstan-3-one + NADPH + H⁺

5alpha-androstane-3beta,17beta-diol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 17beta-hydroxy-5alpha- androstan-3-one + NADPH + H(+)

• Enzyme class 3: E.C.1.1.1.239 - 3alpha-(17beta)-hydroxysteroid dehydrogenase (NAD(+)).
• Reaction: testosterone + NAD⁺ = androst-4-ene-3,17-dione + NADH + H⁺

testosterone (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) + NAD(+) = androst-4-ene-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 + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 3-oxosteroid + NADPH + H(+)

3alpha-hydroxysteroid + 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 + 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 + NADH + H(+)

17beta-estradiol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = estrone + NADPH + H(+)

• Enzyme class 7: E.C.1.1.1.64 - testosterone 17beta-dehydrogenase (NADP(+)).
• Reaction: testosterone + NADP⁺ = androst-4-ene-3,17-dione + NADPH + H⁺

testosterone (Bound ligand (Het Group name = NAP) corresponds exactly) + NADP(+) = androst-4-ene-3,17-dione + 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

Bioorg Med Chem Lett 22:3492-3497 (2012)

PubMed id: 22507964

Crystal structures of AKR1C3 containing an N-(aryl)amino-benzoate inhibitor and a bifunctional AKR1C3 inhibitor and androgen receptor antagonist. Therapeutic leads for castrate resistant prostate cancer.

M.Chen, A.O.Adeniji, B.M.Twenter, J.D.Winkler, D.W.Christianson, T.M.Penning.

ABSTRACT

No abstract given.