PDBsum entry 5jsf

Oxidoreductase

PDB id: 5jsf

Contents

Protein chain

268 a.a.

Ligands

NAD

PGE

Metals

_CL

_NA

Waters ×86

PDB id:

5jsf

Name:

Oxidoreductase

Title:

Crystal structure of 17beta-hydroxysteroid dehydrogenase 14 s205 variant in complex with NAD.

Structure:

17-beta-hydroxysteroid dehydrogenase 14. Chain: a. Synonym: 17-beta-hsd 14,17-beta-hydroxysteroid dehydrogenase dhrs10, dehydrogenase/reductase sdr family member 10,retinal short-chain dehydrogenase/reductase retsdr3,short chain dehydrogenase/reductase family 47c member 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hsd17b14, dhrs10, sdr3, sdr47c1, unq502/pro474. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Expression_system_variant: plyss

Resolution:

1.84Å R-factor: 0.166 R-free: 0.187

Authors:

N.Bertoletti,S.Marchais-Oberwinkler,A.Heine,G.Klebe

Key ref:

N.Bertoletti et al. (2016). New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor. J Med Chem, 59, 6961-6967. PubMed id: 27362750 DOI: 10.1021/acs.jmedchem.6b00293

Date:

08-May-16 Release date: 13-Jul-16

Protein chain

Q9BPX1  (DHB14_HUMAN) -  17-beta-hydroxysteroid dehydrogenase 14 from Homo sapiens

Seq: 270 a.a.

Struc: 268 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: 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 = NAD) corresponds exactly) = estrone + NADH + H(+)

17beta-estradiol + NADP(+) (Bound ligand (Het Group name = NAD) matches with 91.67% similarity) = estrone + NADPH + H(+)

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

reference

DOI no: 10.1021/acs.jmedchem.6b00293

J Med Chem 59:6961-6967 (2016)

PubMed id: 27362750

New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor.

N.Bertoletti, F.Braun, M.Lepage, G.Möller, J.Adamski, A.Heine, G.Klebe, S.Marchais-Oberwinkler.

ABSTRACT

17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding site and are the starting point for structure-based inhibitor design. The two natural variants (S205 and T205) were characterized and adopt a similar structure.