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PDBsum entry 1ral
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Oxidoreductase PDB id
1ral

 

 

 

 

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Contents
Protein chain
308 a.a. *
* Residue conservation analysis
PDB id:
1ral
Name: Oxidoreductase
Title: Three-dimensional structure of rat liver 3alpha-hydroxysteroid(slash) dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily
Structure: 3-alpha-hydroxysteroid dehydrogenase. Chain: a. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116
Resolution:
3.00Å     R-factor:   0.220    
Authors: S.S.Hoog,J.E.Pawlowski,P.M.Alzari,T.M.Penning,M.Lewis
Key ref: S.S.Hoog et al. (1994). Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily. Proc Natl Acad Sci U S A, 91, 2517-2521. PubMed id: 8146147 DOI: 10.1073/pnas.91.7.2517
Date:
04-Feb-94     Release date:   30-Apr-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P23457  (DIDH_RAT) -  3-alpha-hydroxysteroid dehydrogenase from Rattus norvegicus
Seq:
Struc: 		322 a.a.
308 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.50  - 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. a 3alpha-hydroxysteroid + NAD+ = a 3-oxosteroid + NADH + H+
2. a 3alpha-hydroxysteroid + NADP+ = a 3-oxosteroid + NADPH + H+
3alpha-hydroxysteroid
 + NAD(+)
 = 3-oxosteroid
 + NADH
 + H(+)
3alpha-hydroxysteroid
 + NADP(+)
 = 3-oxosteroid
 + NADPH
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1073/pnas.91.7.2517 Proc Natl Acad Sci U S A 91:2517-2521 (1994)
PubMed id: 8146147  
 
 
Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily.
S.S.Hoog, J.E.Pawlowski, P.M.Alzari, T.M.Penning, M.Lewis.
 
  ABSTRACT  
 
The 3.0-A-resolution x-ray structure of rat liver 3 alpha-hydroxysteroid dehydrogenase/dihydrodiol dehydrogenase (3 alpha-HSD, EC 1.1.1.50) was determined by molecular replacement using human placental aldose reductase as the search model. The protein folds into an alpha/beta or triose-phosphate isomerase barrel and lacks a canonical Rossmann fold for binding pyridine nucleotide. The structure contains a concentration of hydrophobic amino acids that lie in a cavity near the top of the barrel and that are presumed to be involved in binding hydrophobic substrates (steroids, prostaglandins, and polycyclic aromatic hydrocarbons) and inhibitors (nonsteroidal antiinflammatory drugs). At the distal end of this cavity lie three residues in close proximity that have been implicated in catalysis by site-directed mutagenesis--Tyr-55, Asp-50, and Lys-84. Tyr-55 is postulated to act as the general acid. 3 alpha-HSD shares significant sequence identity with other HSDs that belong to the aldo-keto reductase superfamily and these may show similar architecture. Other members of this family include prostaglandin F synthase and rho-crystallin. By contrast, 3 alpha-HSD shares no sequence identity with HSDs that are members of the short-chain alcohol dehydrogenase family but does contain the Tyr-Xaa-Xaa-Xaa-Lys consensus sequence implicated in catalysis in this family. In the 3 alpha-HSD structure these residues are on the periphery of the barrel and are unlikely to participate in catalysis.
 

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
  21306562 N.Nagata, Y.Kusakari, Y.Fukunishi, T.Inoue, and Y.Urade (2011).
Catalytic mechanism of the primary human prostaglandin F2α synthase, aldo-keto reductase 1B1--prostaglandin D2 synthase activity in the absence of NADP(H).
  FEBS J, 278, 1288-1298.  
19505496 J.L.Do Rego, J.Y.Seong, D.Burel, J.Leprince, V.Luu-The, K.Tsutsui, M.C.Tonon, G.Pelletier, and H.Vaudry (2009).
Neurosteroid biosynthesis: enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides.
  Front Neuroendocrinol, 30, 259-301.  
18407998 L.Di Costanzo, J.E.Drury, T.M.Penning, and D.W.Christianson (2008).
Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis.
  J Biol Chem, 283, 16830-16839.
PDB codes: 3bur 3buv 3bv7 3cmf 3cot
17575004 H.Jiang, C.Yang, H.Qu, Z.Liu, Q.S.Fu, and C.Qiao (2007).
Cloning of a novel aldo-keto reductase gene from Klebsiella sp. strain F51-1-2 and its functional expression in Escherichia coli.
  Appl Environ Microbiol, 73, 4959-4965.  
  17909281 U.Dhagat, V.Carbone, R.P.Chung, C.Schulze-Briese, S.Endo, A.Hara, and O.El-Kabbani (2007).
Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme from an orthorhombic crystal form: an insight into the bifunctionality of the enzyme.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 825-830.
PDB code: 2p5n
16984997 R.C.Agís-Balboa, G.Pinna, A.Zhubi, E.Maloku, M.Veldic, E.Costa, and A.Guidotti (2006).
Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis.
  Proc Natl Acad Sci U S A, 103, 14602-14607.  
17059222 Y.Jin, and T.M.Penning (2006).
Multiple steps determine the overall rate of the reduction of 5alpha-dihydrotestosterone catalyzed by human type 3 3alpha-hydroxysteroid dehydrogenase: implications for the elimination of androgens.
  Biochemistry, 45, 13054-13063.  
15929998 J.F.Couture, K.P.de Jésus-Tran, A.M.Roy, L.Cantin, P.L.Côté, P.Legrand, V.Luu-The, F.Labrie, and R.Breton (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.
PDB code: 1xjb
15794125 Y.Tsuruo (2005).
Topography and function of androgen-metabolizing enzymes in the central nervous system.
  Anat Sci Int, 80, 1.  
15577260 R.Takenoshita, and S.Toki (2004).
[New aspects of hexobarbital metabolism: stereoselective metabolism, new metabolic pathway via GSH conjugation, and 3-hydroxyhexobarbital dehydrogenases]
  Yakugaku Zasshi, 124, 857-871.  
15038957 T.M.Penning (2004).
Aldo-keto reductases and formation of polycyclic aromatic hydrocarbon o-quinones.
  Methods Enzymol, 378, 31-67.  
12554958 A.Ehrensberger, and D.K.Wilson (2003).
Expression, crystallization and activities of the two family 11 aldo-keto reductases from Bacillus subtilis.
  Acta Crystallogr D Biol Crystallogr, 59, 375-377.  
14517983 G.Obmolova, A.Teplyakov, P.P.Khil, A.J.Howard, R.D.Camerini-Otero, and G.L.Gilliland (2003).
Crystal structure of the Escherichia coli Tas protein, an NADP(H)-dependent aldo-keto reductase.
  Proteins, 53, 323-325.
PDB code: 1lqa
12416991 J.W.Trauger, A.Jiang, B.A.Stearns, and P.V.LoGrasso (2002).
Kinetics of allopregnanolone formation catalyzed by human 3 alpha-hydroxysteroid dehydrogenase type III (AKR1C2).
  Biochemistry, 41, 13451-13459.  
12218169 M.L.Baker, I.I.Serysheva, S.Sencer, Y.Wu, S.J.Ludtke, W.Jiang, S.L.Hamilton, and W.Chiu (2002).
The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain.
  Proc Natl Acad Sci U S A, 99, 12155-12160.  
11306077 B.Nidetzky, P.Mayr, W.Neuhauser, and M.Puchberger (2001).
Structural and functional properties of aldose xylose reductase from the D-xylose-metabolizing yeast Candida tenuis.
  Chem Biol Interact, 130, 583-595.  
11306101 R.Takenoshita, Y.Nomura, and S.Toki (2001).
Cloning and expression of cDNA encoding hamster liver 3-hydroxyhexobarbital/17beta(3alpha)-hydroxysteroid dehydrogenase 1.
  Chem Biol Interact, 130, 863-870.  
10818358 E.Hur, and D.K.Wilson (2000).
Crystallization and aldo-keto reductase activity of Gcy1p from Saccharomyces cerevisiae.
  Acta Crystallogr D Biol Crystallogr, 56, 763-765.  
11025551 O.El-Kabbani, H.Rogniaux, P.Barth, R.P.Chung, E.V.Fletcher, A.Van Dorsselaer, and A.Podjarny (2000).
Aldose and aldehyde reductases: correlation of molecular modeling and mass spectrometric studies on the binding of inhibitors to the active site.
  Proteins, 41, 407-414.  
10651037 Q.Ye, D.Hyndman, X.Li, T.G.Flynn, and Z.Jia (2000).
Crystal structure of CHO reductase, a member of the aldo-keto reductase superfamily.
  Proteins, 38, 41-48.
PDB code: 1c9w
10737928 S.Khurana, G.Sanli, D.B.Powers, S.Anderson, and M.Blaber (2000).
Molecular modeling of substrate binding in wild-type and mutant Corynebacteria 2,5-diketo-D-gluconate reductases.
  Proteins, 39, 68-75.  
10500147 H.Ma, and T.M.Penning (1999).
Conversion of mammalian 3alpha-hydroxysteroid dehydrogenase to 20alpha-hydroxysteroid dehydrogenase using loop chimeras: changing specificity from androgens to progestins.
  Proc Natl Acad Sci U S A, 96, 11161-11166.  
10387026 K.Ratnam, H.Ma, and T.M.Penning (1999).
The arginine 276 anchor for NADP(H) dictates fluorescence kinetic transients in 3 alpha-hydroxysteroid dehydrogenase, a representative aldo-keto reductase.
  Biochemistry, 38, 7856-7864.  
9521675 B.P.Schlegel, J.M.Jez, and T.M.Penning (1998).
Mutagenesis of 3 alpha-hydroxysteroid dehydrogenase reveals a "push-pull" mechanism for proton transfer in aldo-keto reductases.
  Biochemistry, 37, 3538-3548.  
9692994 B.P.Schlegel, K.Ratnam, and T.M.Penning (1998).
Retention of NADPH-linked quinone reductase activity in an aldo-keto reductase following mutation of the catalytic tyrosine.
  Biochemistry, 37, 11003-11011.  
9521731 J.Luba, B.Nare, P.H.Liang, K.S.Anderson, S.M.Beverley, and L.W.Hardy (1998).
Leishmania major pteridine reductase 1 belongs to the short chain dehydrogenase family: stereochemical and kinetic evidence.
  Biochemistry, 37, 4093-4104.  
9657682 J.M.Jez, and T.M.Penning (1998).
Engineering steroid 5 beta-reductase activity into rat liver 3 alpha-hydroxysteroid dehydrogenase.
  Biochemistry, 37, 9695-9703.  
9618487 S.Khurana, D.B.Powers, S.Anderson, and M.Blaber (1998).
Crystal structure of 2,5-diketo-D-gluconic acid reductase A complexed with NADPH at 2.1-A resolution.
  Proc Natl Acad Sci U S A, 95, 6768-6773.
PDB code: 1a80
9261071 M.J.Bennett, R.H.Albert, J.M.Jez, H.Ma, T.M.Penning, and M.Lewis (1997).
Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase.
  Structure, 5, 799-812.
PDB code: 1afs
9095201 Z.J.Liu, Y.J.Sun, J.Rose, Y.J.Chung, C.D.Hsiao, W.R.Chang, I.Kuo, J.Perozich, R.Lindahl, J.Hempel, and B.C.Wang (1997).
The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold.
  Nat Struct Biol, 4, 317-326.
PDB code: 1ad3
8718859 M.J.Bennett, B.P.Schlegel, J.M.Jez, T.M.Penning, and M.Lewis (1996).
Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+.
  Biochemistry, 35, 10702-10711.
PDB code: 1lwi
  8762144 S.Janecek (1996).
Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?
  Protein Sci, 5, 1136-1143.  
8944761 U.C.Oppermann, and E.Maser (1996).
Characterization of a 3 alpha-hydroxysteroid dehydrogenase/carbonyl reductase from the gram-negative bacterium Comamonas testosteroni.
  Eur J Biochem, 241, 744-749.  
8994882 W.L.Duax, J.F.Griffin, and D.Ghosh (1996).
The fascinating complexities of steroid-binding enzymes.
  Curr Opin Struct Biol, 6, 813-823.  
7542775 S.W.Chouinard, G.F.Wilson, A.K.Schlimgen, and B.Ganetzky (1995).
A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus.
  Proc Natl Acad Sci U S A, 92, 6763-6767.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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