PDBsum entry 1xjb

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Oxidoreductase PDB id
Jmol PyMol
Protein chain
325 a.a. *
ACT ×3
NAP ×2
EDO ×2
SO4 ×2
Waters ×477
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of human type 3 3alpha-hydroxysteroid dehy in complex with NADP(h), citrate and acetate molecules
Structure: Aldo-keto reductase family 1 member c2. Chain: a, b. Synonym: h3alphahsd3. Trans-1,2- dihydrobenzene-1,2-diol dehydrogenase. Chlordecone reductase homolog hakrd. Dihydro dehydrogenase/bile acid-binding protein. Dd/babp. Dihydrodi dehydrogenase 2. Dd2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: akr1c2, ddh2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hexamer (from PQS)
1.90Å     R-factor:   0.175     R-free:   0.199
Authors: J.-F.Couture,K.Pereira De Jesus-Tran,A.-M.Roy,P.Legrand,L.Ca L.Cote,V.Luu-The,F.Labrie,R.Breton
Key ref:
J.F.Couture et al. (2005). Comparison of crystal structures of human type 3 3alpha-hydroxysteroid dehydrogenase reveals an "induced-fit" mechanism and a conserved basic motif involved in the binding of androgen. Protein Sci, 14, 1485-1497. PubMed id: 15929998 DOI: 10.1110/ps.051353205
23-Sep-04     Release date:   21-Jun-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P52895  (AK1C2_HUMAN) -  Aldo-keto reductase family 1 member C2
323 a.a.
325 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.  - 3-alpha-hydroxysteroid 3-dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A 3-alpha-hydroxysteroid + NAD(P)(+) = a 3-oxosteroid + NAD(P)H
Bound ligand (Het Group name = NAP)
corresponds exactly
= 3-oxosteroid
   Enzyme class 2: E.C.  - Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Trans-1,2-dihydrobenzene-1,2-diol + NADP+ = catechol + NADPH
Bound ligand (Het Group name = CIT)
matches with 40.00% similarity
Bound ligand (Het Group name = NAP)
corresponds exactly
= catechol
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     daunorubicin metabolic process   14 terms 
  Biochemical function     oxidoreductase activity     8 terms  


DOI no: 10.1110/ps.051353205 Protein Sci 14:1485-1497 (2005)
PubMed id: 15929998  
Comparison of crystal structures of human type 3 3alpha-hydroxysteroid dehydrogenase reveals an "induced-fit" mechanism and a conserved basic motif involved in the binding of androgen.
J.F.Couture, Jésus-Tran, A.M.Roy, L.Cantin, P.L.Côté, P.Legrand, V.Luu-The, F.Labrie, R.Breton.
The aldo-keto reductase (AKR) human type 3 3alpha-hydroxysteroid dehydrogenase (h3alpha-HSD3, AKR1C2) plays a crucial role in the regulation of the intracellular concentrations of testosterone and 5alpha-dihydrotestosterone (5alpha-DHT), two steroids directly linked to the etiology and the progression of many prostate diseases and cancer. This enzyme also binds many structurally different molecules such as 4-hydroxynonenal, polycyclic aromatic hydrocarbons, and indanone. To understand the mechanism underlying the plasticity of its substrate-binding site, we solved the binary complex structure of h3alpha-HSD3-NADP(H) at 1.9 A resolution. During the refinement process, we found acetate and citrate molecules deeply engulfed in the steroid-binding cavity. Superimposition of this structure with the h3alpha-HSD3-NADP(H)-testosterone/acetate ternary complex structure reveals that one of the mobile loops forming the binding cavity operates a slight contraction movement against the citrate molecule while the side chains of many residues undergo numerous conformational changes, probably to create an optimal binding site for the citrate. These structural changes, which altogether cause a reduction of the substrate-binding cavity volume (from 776 A(3) in the presence of testosterone/acetate to 704 A(3) in the acetate/citrate complex), are reminiscent of the "induced-fit" mechanism previously proposed for the aldose reductase, another member of the AKR superfamily. We also found that the replacement of residues Arg(301) and Arg(304), localized near the steroid-binding cavity, significantly affects the 3alpha-HSD activity of this enzyme toward 5alpha-DHT and completely abolishes its 17beta-HSD activity on 4-dione. All these results have thus been used to reevaluate the binding mode of this enzyme for androgens.
  Selected figure(s)  
Figure 1.
Figure 1. Schematic representation of enzymatic properties of HSDs member of the AKR superfamily. (A) Reactions catalyzed by h3 -HSD3 on 4-dione and DHT. (B) Overview of the molecules that bind and/or are transformed by HSDs member of the AKR superfamily (the figure has been created with SwissPDBViewer and rendered with Povray; Kaplan and Littlejohn 2001). (C) Orbital steering constraints proposed by Heredia et al. (2003). Here, the optimal distance from the catalytic Tyr residue, the angle of the hydride with the target ketone (in parentheses), and the distance of the C4 of the pyridine head of the cofactor are indicated (created with Molscript and POVScript; Kraulis 1991; Fenn et al. 2003).
Figure 4.
Figure 4. Stereo view of the hypothetic orientation of two different androgens for their optimal reduction by h3 -HSD3. The target ketone group of 4-dione (light gray) and DHT (dark gray) were manually superimposed on the acetate molecule. Only residues in proximity of the steroid are depicted. Figure was created with POVScript (Fenn et al. 2003) and rendered with Pov-Ray (Kaplan and Littlejohn 2001).
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2005, 14, 1485-1497) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21217827 J.W.Arthur, and J.K.Reichardt (2010).
Modeling single nucleotide polymorphisms in the human AKR1C1 and AKR1C2 genes: implications for functional and genotyping analyses.
  PLoS One, 5, e15604.  
18224704 S.Karkola, A.Lilienkampf, and K.Wähälä (2008).
A 3D QSAR model of 17beta-HSD1 inhibitors based on a thieno[2,3-d]pyrimidin-4(3H)-one core applying molecular dynamics simulations and ligand-protein docking.
  ChemMedChem, 3, 461-472.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.