PDBsum entry 3nty

Oxidoreductase/oxidoreductase inhibitor

PDB id: 3nty

Contents

Protein chain

318 a.a.

Ligands

NAP

5P3

Metals

_ZN

Waters ×379

PDB id:

3nty

Name:

Oxidoreductase/oxidoreductase inhibitor

Title:

Crystal structure of akr1c1 in complex with NADP and 5-phenyl,3- chlorosalicylic acid

Structure:

Aldo-keto reductase family 1 member c1. Chain: a. Synonym: akr1c1, 20-alpha-hydroxysteroid dehydrogenase, 20-alpha-hsd, trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, indanol dehydrogenase, dihydrodiol dehydrogenase 1/2, dd1/dd2, chlordecone reductase homolog hakrc, high-affinity hepatic bile acid-binding protein, hbab. Ec: 1.1.1.-, 1.1.1.149, 1.3.1.20, 1.1.1.112. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.87Å R-factor: 0.188 R-free: 0.253

Authors:

U.Dhagat,O.El-Kabbani

Key ref:

O.El-Kabbani et al. (2011). Probing the inhibitor selectivity pocket of human 20α-hydroxysteroid dehydrogenase (AKR1C1) with X-ray crystallography and site-directed mutagenesis. Bioorg Med Chem Lett, 21, 2564-2567. PubMed id: 21414777

Date:

06-Jul-10 Release date: 13-Apr-11

Protein chain

Q04828  (AK1C1_HUMAN) -  Aldo-keto reductase family 1 member C1 from Homo sapiens

Seq: 323 a.a.

Struc: 318 a.a.

Enzyme reactions

• Enzyme class 1: 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 2: E.C.1.1.1.149 - 20alpha-hydroxysteroid dehydrogenase.
• Reaction:
  1. (17R,20S)-17,20-dihydroxypregn-4-en-3-one + NAD⁺ = 17alpha- hydroxyprogesterone + NADH + H⁺
  2. (17R,20S)-17,20-dihydroxypregn-4-en-3-one + NADP⁺ = 17alpha- hydroxyprogesterone + NADPH + H⁺

(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 17alpha- hydroxyprogesterone (Bound ligand (Het Group name = 5P3) matches with 51.85% similarity) + NADH + H(+)

(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 17alpha- hydroxyprogesterone (Bound ligand (Het Group name = 5P3) matches with 51.85% similarity) + 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 = 5P3) matches with 58.33% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 5alpha-androstan-3,17-dione + NADPH + H(+)

androsterone (Bound ligand (Het Group name = 5P3) matches with 58.33% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 5alpha-androstan-3,17-dione + NADH + H(+)

• Enzyme class 4: E.C.1.1.1.210 - 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 (Bound ligand (Het Group name = 5P3) matches with 58.33% similarity) + NADPH + H(+)

• Enzyme class 5: 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 = 5P3) matches with 60.87% similarity) + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = 3-oxosteroid + NADPH + H(+)

3alpha-hydroxysteroid (Bound ligand (Het Group name = 5P3) matches with 60.87% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 3-oxosteroid + NADH + H(+)

• Enzyme class 6: E.C.1.1.1.51 - 3(or 17)beta-hydroxysteroid dehydrogenase.
• Reaction:
  1. testosterone + NAD⁺ = androst-4-ene-3,17-dione + NADH + H⁺
  2. testosterone + NADP⁺ = androst-4-ene-3,17-dione + NADPH + H⁺

testosterone (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) + NAD(+) (Bound ligand (Het Group name = 5P3) matches with 58.33% similarity) = androst-4-ene-3,17-dione + NADH + H(+)

testosterone (Bound ligand (Het Group name = NAP) corresponds exactly) + NADP(+) (Bound ligand (Het Group name = 5P3) matches with 58.33% similarity) = androst-4-ene-3,17-dione + NADPH + H(+)

• Enzyme class 7: 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 = 5P3) matches with 58.33% similarity) + NAD(+) (Bound ligand (Het Group name = NAP) matches with 91.67% similarity) = 17beta-hydroxyandrostanone + NADH + H(+)

• Enzyme class 8: 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 = 5P3) matches with 60.87% similarity) + NADH + H(+)

17beta-estradiol + NADP(+) (Bound ligand (Het Group name = NAP) corresponds exactly) = estrone (Bound ligand (Het Group name = 5P3) matches with 60.87% similarity) + NADPH + H(+)

• Enzyme class 9: 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

Bioorg Med Chem Lett 21:2564-2567 (2011)

PubMed id: 21414777

Probing the inhibitor selectivity pocket of human 20α-hydroxysteroid dehydrogenase (AKR1C1) with X-ray crystallography and site-directed mutagenesis.

O.El-Kabbani, U.Dhagat, M.Soda, S.Endo, T.Matsunaga, A.Hara.

ABSTRACT

No abstract given.