spacer
spacer

PDBsum entry 1ae4
Go to PDB code: 
protein ligands links
Oxidoreductase PDB id
1ae4
Contents
Protein chain
324 a.a.* *
Ligands
NAP
TOL
* Residue conservation analysis
* C-alpha coords only
PDB id:
1ae4
Name: Oxidoreductase
Title: Aldehyde reductase complexed with cofactor and inhibitor, alpha carbon atoms only
Structure: Aldehyde reductase. Chain: a. Synonym: alr1. Ec: 1.1.1.2
Source: Sus scrofa. Pig. Organism_taxid: 9823. Organ: kidney. Tissue: medulla, cortex
Resolution:
2.40Å     R-factor:   0.190    
Authors: O.El-Kabbani
Key ref: O.el-Kabbani et al. (1997). Studies on the inhibitor-binding site of porcine aldehyde reductase: crystal structure of the holoenzyme-inhibitor ternary complex. Proteins, 29, 186-192. PubMed id: 9329083
Date:
05-Mar-97     Release date:   11-Mar-98    
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P50578  (AK1A1_PIG) -  Aldo-keto reductase family 1 member A1 from Sus scrofa
Seq:
Struc: 		325 a.a.
324 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: E.C.1.1.1.19  - glucuronate reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Mammalian Ascorbic Acid Biosynthesis
      Reaction: L-gulonate + NADP+ = aldehydo-D-glucuronate + NADPH + H+
L-gulonate
 +
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly 		= aldehydo-D-glucuronate
 + NADPH
 + H(+)
   Enzyme class 2: E.C.1.1.1.2  - alcohol dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: a primary alcohol + NADP+ = an aldehyde + NADPH + H+
primary alcohol
 +
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly 		= aldehyde
 + NADPH
 + H(+)
      Cofactor: Zn(2+)
   Enzyme class 3: E.C.1.1.1.20  - glucuronolactone reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-gulono-1,4-lactone + NADP+ = D-glucurono-3,6-lactone + NADPH + H+
L-gulono-1,4-lactone
 +
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly 		= D-glucurono-3,6-lactone
 + NADPH
 + H(+)
   Enzyme class 4: E.C.1.1.1.372  - D/L-glyceraldehyde reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. glycerol + NADP+ = L-glyceraldehyde + NADPH + H+
2. glycerol + NADP+ = D-glyceraldehyde + NADPH + H+
glycerol
 +
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly 		= L-glyceraldehyde
 + NADPH
 + H(+)
glycerol
 +
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly 		= D-glyceraldehyde
 + NADPH
 + H(+)
   Enzyme class 5: E.C.1.1.1.54  - allyl-alcohol dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: allyl alcohol + NADP+ = acrolein + NADPH + H+
allyl alcohol
 +
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly 		= acrolein
 + 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    
 
 
Proteins 29:186-192 (1997)
PubMed id: 9329083  
 
 
Studies on the inhibitor-binding site of porcine aldehyde reductase: crystal structure of the holoenzyme-inhibitor ternary complex.
O.el-Kabbani, D.A.Carper, M.H.McGowan, Y.Devedjiev, K.J.Rees-Milton, T.G.Flynn.
 
  ABSTRACT  
 
Aldehyde reductase is an enzyme capable of metabolizing a wide variety of aldehydes to their corresponding alcohols. The tertiary structures of aldehyde reductase and aldose reductase are similar and consist of an alpha/beta-barrel with the active site located at the carboxy terminus of the strands of the barrel. We have determined the X-ray crystal structure of porcine aldehyde reductase holoenzyme in complex with an aldose reductase inhibitor, tolrestat, at 2.4 A resolution to obtain a picture of the binding conformation of inhibitors to aldehyde reductase. Tolrestat binds in the active site pocket of aldehyde reductase and interacts through van der Waals contacts with Arg 312 and Asp 313. The carboxylate group of tolrestat is within hydrogen bonding distance with His 113 and Trp 114. Mutation of Arg 312 to alanine in porcine aldehyde reductase alters the potency of inhibition of the enzyme by aldose reductase inhibitors. Our results indicate that the structure of the inhibitor-binding site of aldehyde reductase differs from that of aldose reductase due to the participation of nonconserved residues in its formation. A major difference is the participation of Arg 312 and Asp 313 in lining the inhibitor-binding site in aldehyde reductase but not in aldose reductase.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21365086 E.Parisini, P.Metrangolo, T.Pilati, G.Resnati, and G.Terraneo (2011).
Halogen bonding in halocarbon-protein complexes: a structural survey.
  Chem Soc Rev, 40, 2267-2278.  
21414777 O.El-Kabbani, U.Dhagat, M.Soda, S.Endo, T.Matsunaga, and A.Hara (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.
PDB code: 3nty
15146478 E.I.Howard, R.Sanishvili, R.E.Cachau, A.Mitschler, B.Chevrier, P.Barth, V.Lamour, M.Van Zandt, E.Sibley, C.Bon, D.Moras, T.R.Schneider, A.Joachimiak, and A.Podjarny (2004).
Ultrahigh resolution drug design I: details of interactions in human aldose reductase-inhibitor complex at 0.66 A.
  Proteins, 55, 792-804.
PDB code: 1us0
14551196 K.Ehrenman, G.Yang, W.P.Hong, T.Gao, W.Jang, D.A.Brock, R.D.Hatton, J.D.Shoemaker, and R.H.Gomer (2004).
Disruption of aldehyde reductase increases group size in dictyostelium.
  J Biol Chem, 279, 837-847.  
15146479 O.El-Kabbani, C.Darmanin, T.R.Schneider, I.Hazemann, F.Ruiz, M.Oka, A.Joachimiak, C.Schulze-Briese, T.Tomizaki, A.Mitschler, and A.Podjarny (2004).
Ultrahigh resolution drug design. II. Atomic resolution structures of human aldose reductase holoenzyme complexed with Fidarestat and Minalrestat: implications for the binding of cyclic imide inhibitors.
  Proteins, 55, 805-813.
PDB codes: 1pwl 1pwm
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
12486717 O.El-Kabbani, P.Ramsland, C.Darmanin, R.P.Chung, and A.Podjarny (2003).
Structure of human aldose reductase holoenzyme in complex with statil: an approach to structure-based inhibitor design of the enzyme.
  Proteins, 50, 230-238.  
11354001 Q.Ye, D.Hyndman, N.Green, X.Li, B.Korithoski, Z.Jia, and T.G.Flynn (2001).
Crystal structure of an aldehyde reductase Y50F mutant-NADP complex and its implications for substrate binding.
  Proteins, 44, 12-19.  
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.  
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.

 

spacer
spacer