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Oxidoreductase PDB id
1abn
Jmol
Contents
Protein chain
301 a.a.* *
Ligands
NDP
* Residue conservation analysis
* C-alpha coords only
PDB id:
1abn
Name: Oxidoreductase
Title: The crystal structure of the aldose reductase NADPH binary complex
Structure: Aldose reductase. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.40Å     R-factor:   0.286    
Authors: D.W.Borhani,T.M.Harter,J.M.Petrash
Key ref: D.W.Borhani et al. (1992). The crystal structure of the aldose reductase.NADPH binary complex. J Biol Chem, 267, 24841-24847. PubMed id: 1447221
Date:
03-Sep-92     Release date:   31-Jan-94    
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P15121  (ALDR_HUMAN) -  Aldose reductase
Seq:
Struc: 		316 a.a.
301 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.21  - Aldehyde reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Alditol + NAD(P)(+) = aldose + NAD(P)H
Alditol
 +
NAD(P)(+)
Bound ligand (Het Group name = NDP)
corresponds exactly 		= aldose
 + NAD(P)H
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   3 terms 
  Biological process     response to stress   4 terms 
  Biochemical function     electron carrier activity     5 terms  

 

 
    reference    
 
 
J Biol Chem 267:24841-24847 (1992)
PubMed id: 1447221  
 
 
The crystal structure of the aldose reductase.NADPH binary complex.
D.W.Borhani, T.M.Harter, J.M.Petrash.
 
  ABSTRACT  
 
Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a broad range of aldehydes, including glucose. Since aldose reductase has been strongly implicated in the development of the chronic complications of diabetes mellitus, much effort has been devoted to understanding the structure and mechanism of this enzyme, and many aldose reductase inhibitors have been developed as potential drugs for the treatment of these complications. We describe here the 2.75 A crystal structure of recombinant human aldose reductase (Cys-298 to Ser mutant) complexed with NADPH. This mutant displays unusual kinetic behavior characterized by high Km/high Vmax substrate kinetics and reduced sensitivity to certain aldose reductase inhibitors. The crystal structure revealed that the enzyme is a beta/alpha-barrel with the coenzyme-binding domain located at the carboxyl-terminal end of the parallel strands of the barrel. The enzyme undergoes a large conformational change upon binding NADPH which involves the reorientation of loop 7 to a position which appears to lock the coenzyme into place. NADPH is bound to aldose reductase in an unusual manner, more similar to FAD- rather than NAD(P)-dependent oxidoreductases. No disulfide bridges were observed in the crystal structure.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20529366 D.H.Lee, Y.J.Lee, Y.W.Ryu, and J.H.Seo (2010).
Molecular cloning and biochemical characterization of a novel erythrose reductase from Candida magnoliae JH110.
  Microb Cell Fact, 9, 43.  
20124700 U.Dhagat, S.Endo, H.Mamiya, A.Hara, and O.El-Kabbani (2010).
Studies on a Tyr residue critical for the binding of coenzyme and substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21): structure of the Y224D mutant enzyme.
  Acta Crystallogr D Biol Crystallogr, 66, 198-204.
PDB code: 3fjn
17505104 M.Biadene, I.Hazemann, A.Cousido, S.Ginell, A.Joachimiak, G.M.Sheldrick, A.Podjarny, and T.R.Schneider (2007).
The atomic resolution structure of human aldose reductase reveals that rearrangement of a bound ligand allows the opening of the safety-belt loop.
  Acta Crystallogr D Biol Crystallogr, 63, 665-672.
PDB code: 2j8t
16391048 R.Machielsen, A.R.Uria, S.W.Kengen, and J.van der Oost (2006).
Production and characterization of a thermostable alcohol dehydrogenase that belongs to the aldo-keto reductase superfamily.
  Appl Environ Microbiol, 72, 233-238.  
15146480 O.Kraemer, I.Hazemann, A.D.Podjarny, and G.Klebe (2004).
Virtual screening for inhibitors of human aldose reductase.
  Proteins, 55, 814-823.  
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
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.  
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
10384727 H.Rogniaux, A.Van Dorsselaer, P.Barth, J.F.Biellmann, J.Barbanton, M.van Zandt, B.Chevrier, E.Howard, A.Mitschler, N.Potier, L.Urzhumtseva, D.Moras, and A.Podjarny (1999).
Binding of aldose reductase inhibitors: correlation of crystallographic and mass spectrometric studies.
  J Am Soc Mass Spectrom, 10, 635-647.  
10399921 J.M.Gulbis, S.Mann, and R.MacKinnon (1999).
Structure of a voltage-dependent K+ channel beta subunit.
  Cell, 97, 943-952.
PDB code: 1qrq
9918192 L.Costantino, G.Rastelli, P.Vianello, G.Cignarella, and D.Barlocco (1999).
Diabetes complications and their potential prevention: aldose reductase inhibition and other approaches.
  Med Res Rev, 19, 3.  
  10493576 M.Young, K.Kirshenbaum, K.A.Dill, and S.Highsmith (1999).
Predicting conformational switches in proteins.
  Protein Sci, 8, 1752-1764.  
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.  
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
9737870 S.Srivastava, T.M.Harter, A.Chandra, A.Bhatnagar, S.K.Srivastava, and J.M.Petrash (1998).
Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase.
  Biochemistry, 37, 12909-12917.  
9454604 W.Neuhauser, D.Haltrich, K.D.Kulbe, and B.Nidetzky (1998).
Noncovalent enzyme-substrate interactions in the catalytic mechanism of yeast aldose reductase.
  Biochemistry, 37, 1116-1123.  
  9195881 A.Urzhumtsev, F.Tête-Favier, A.Mitschler, J.Barbanton, P.Barth, L.Urzhumtseva, J.F.Biellmann, A.Podjarny, and D.Moras (1997).
A 'specificity' pocket inferred from the crystal structures of the complexes of aldose reductase with the pharmaceutically important inhibitors tolrestat and sorbinil.
  Structure, 5, 601-612.
PDB codes: 1ah0 1ah3 1ah4
  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
  8779568 K.Kita, K.Matsuzaki, T.Hashimoto, H.Yanase, N.Kato, M.C.Chung, M.Kataoka, and S.Shimizu (1996).
Cloning of the aldehyde reductase gene from a red yeast, Sporobolomyces salmonicolor, and characterization of the gene and its product.
  Appl Environ Microbiol, 62, 2303-2310.  
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
  8805511 N.Tanaka, T.Nonaka, M.Nakanishi, Y.Deyashiki, A.Hara, and Y.Mitsui (1996).
Crystal structure of the ternary complex of mouse lung carbonyl reductase at 1.8 A resolution: the structural origin of coenzyme specificity in the short-chain dehydrogenase/reductase family.
  Structure, 4, 33-45.
PDB code: 1cyd
8780524 T.Nakano, and J.M.Petrash (1996).
Kinetic and spectroscopic evidence for active site inhibition of human aldose reductase.
  Biochemistry, 35, 11196-11202.  
7811733 D.A.Carper, T.C.Hohman, and S.E.Old (1995).
Residues affecting the catalysis and inhibition of rat lens aldose reductase.
  Biochim Biophys Acta, 1246, 67-73.  
  7663348 M.Gondry, K.H.Diêp Lê, F.D.Manson, S.K.Chapman, F.S.Mathews, G.A.Reid, and F.Lederer (1995).
On the lack of coordination between protein folding and flavin insertion in Escherichia coli for flavocytochrome b2 mutant forms Y254L and D282N.
  Protein Sci, 4, 925-935.  
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.  
8048162 D.Bossemeyer (1994).
The glycine-rich sequence of protein kinases: a multifunctional element.
  Trends Biochem Sci, 19, 201-205.  
8146147 S.S.Hoog, J.E.Pawlowski, P.M.Alzari, T.M.Penning, and M.Lewis (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.
PDB code: 1ral
8234324 D.K.Wilson, I.Tarle, J.M.Petrash, and F.A.Quiocho (1993).
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat.
  Proc Natl Acad Sci U S A, 90, 9847-9851.
PDB code: 1mar
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 code is shown on the right.