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PDBsum entry 1ee2

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1ee2
Jmol
Contents
Protein chains
373 a.a. *
Ligands
NAD ×2
CHD ×2
Metals
_ZN ×4
Waters ×1010
* Residue conservation analysis
PDB id:
1ee2
Name: Oxidoreductase
Title: The structure of steroid-active alcohol dehydrogenase at 1.5 resolution
Structure: Alcohol dehydrogenase. Chain: a, b. Ec: 1.1.1.1
Source: Equus caballus. Horse. Organism_taxid: 9796. Organ: liver
Biol. unit: Dimer (from PQS)
Resolution:
1.54Å     R-factor:   0.148     R-free:   0.183
Authors: H.W.Adolph
Key ref:
H.W.Adolph et al. (2000). Structural basis for substrate specificity differences of horse liver alcohol dehydrogenase isozymes. Biochemistry, 39, 12885-12897. PubMed id: 11041853 DOI: 10.1021/bi001376s
Date:
30-Jan-00     Release date:   27-Oct-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00328  (ADH1S_HORSE) -  Alcohol dehydrogenase S chain
Seq:
Struc:
374 a.a.
373 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.1  - Alcohol dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. An alcohol + NAD+ = an aldehyde or ketone + NADH
2. A secondary alcohol + NAD+ = a ketone + NADH
alcohol
+
NAD(+)
Bound ligand (Het Group name = NAD)
corresponds exactly
= aldehyde or ketone
+ NADH
secondary alcohol
+ NAD(+)
= ketone
+ NADH
      Cofactor: Zn(2+) or Fe cation
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     oxidation-reduction process   1 term 
  Biochemical function     oxidoreductase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi001376s Biochemistry 39:12885-12897 (2000)
PubMed id: 11041853  
 
 
Structural basis for substrate specificity differences of horse liver alcohol dehydrogenase isozymes.
H.W.Adolph, P.Zwart, R.Meijers, I.Hubatsch, M.Kiefer, V.Lamzin, E.Cedergren-Zeppezauer.
 
  ABSTRACT  
 
A structure determination in combination with a kinetic study of the steroid converting isozyme of horse liver alcohol dehydrogenase, SS-ADH, is presented. Kinetic parameters for the substrates, 5beta-androstane-3beta,17beta-ol, 5beta-androstane-17beta-ol-3-one, ethanol, and various secondary alcohols and the corresponding ketones are compared for the SS- and EE-isozymes which differ by nine amino acid substitutions and one deletion. Differences in substrate specificity and stereoselectivity are explained on the basis of individual kinetic rate constants for the underlying ordered bi-bi mechanism. SS-ADH was crystallized in complex with 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan -24-acid (cholic acid) and NAD(+), but microspectrophotometric analysis of single crystals proved it to be a mixed complex containing 60-70% NAD(+) and 30-40% NADH. The crystals belong to the space group P2(1) with cell dimensions a = 55.0 A, b = 73.2 A, c = 92.5 A, and beta = 102.5 degrees. A 98% complete data set to 1.54-A resolution was collected at 100 K using synchrotron radiation. The structure was solved by the molecular replacement method utilizing EE-ADH as the search model. The major structural difference between the isozymes is a widening of the substrate channel. The largest shifts in C(alpha) carbon positions (about 5 A) are observed in the loop region, in which a deletion of Asp115 is found in the SS isozyme. SS-ADH easily accommodates cholic acid, whereas steroid substrates of similar bulkiness would not fit into the EE-ADH substrate site. In the ternary complex with NAD(+)/NADH, we find that the carboxyl group of cholic acid ligates to the active site zinc ion, which probably contributes to the strong binding in the ternary NAD(+) complex.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19444390 A.Barzegar, A.A.Moosavi-Movahedi, A.Kyani, B.Goliaei, S.Ahmadian, and N.Sheibani (2010).
New model for polymerization of oligomeric alcohol dehydrogenases into nanoaggregates.
  Appl Biochem Biotechnol, 160, 1188-1205.  
19583966 B.V.Plapp (2010).
Conformational changes and catalysis by alcohol dehydrogenase.
  Arch Biochem Biophys, 493, 3.  
19058034 E.N.Marino-Marmolejo, A.De León-Rodríguez, A.P.de la Rosa, and L.Santos (2009).
Heterologous Expression and Characterization of an Alcohol Dehydrogenase from the Archeon Thermoplasma acidophilum.
  Mol Biotechnol, 42, 61-67.  
17485854 N.Lertwattanasakul, K.Sootsuwan, S.Limtong, P.Thanonkeo, and M.Yamada (2007).
Comparison of the gene expression patterns of alcohol dehydrogenase isozymes in the thermotolerant yeast Kluyveromyces marxianus and their physiological functions.
  Biosci Biotechnol Biochem, 71, 1170-1182.  
16204887 J.Aishima, D.S.Russel, L.J.Guibas, P.D.Adams, and A.T.Brunger (2005).
Automated crystallographic ligand building using the medial axis transform of an electron-density isosurface.
  Acta Crystallogr D Biol Crystallogr, 61, 1354-1363.  
15536071 U.Heinz, M.Kiefer, A.Tholey, and H.W.Adolph (2005).
On the competition for available zinc.
  J Biol Chem, 280, 3197-3207.  
  16233615 H.Hirakawa, N.Kamiya, Y.Kawarabayashi, and T.Nagamune (2004).
Properties of an alcohol dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix K1.
  J Biosci Bioeng, 97, 202-206.  
15292121 J.E.Bidlack, and P.M.Silverman (2004).
An active type IV secretion system encoded by the F plasmid sensitizes Escherichia coli to bile salts.
  J Bacteriol, 186, 5202-5209.  
15572776 P.H.Zwart, G.G.Langer, and V.S.Lamzin (2004).
Modelling bound ligands in protein crystal structures.
  Acta Crystallogr D Biol Crystallogr, 60, 2230-2239.  
12554944 E.Valencia, A.Rosell, C.Larroy, J.Farrés, J.A.Biosca, I.Fita, X.Parés, and W.F.Ochoa (2003).
Crystallization and preliminary X-ray analysis of NADP(H)-dependent alcohol dehydrogenases from Saccharomyces cerevisiae and Rana perezi.
  Acta Crystallogr D Biol Crystallogr, 59, 334-337.  
12192068 C.A.Bottoms, P.E.Smith, and J.J.Tanner (2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
  Protein Sci, 11, 2125-2137.  
11997393 C.F.Chou, C.L.Lai, Y.C.Chang, G.Duester, and S.J.Yin (2002).
Kinetic mechanism of human class IV alcohol dehydrogenase functioning as retinol dehydrogenase.
  J Biol Chem, 277, 25209-25216.  
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.