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PDBsum entry 1p0c
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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1p0c

 

 

 

 

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Contents
Protein chains
372 a.a. *
Ligands
PO4 ×2
GOL ×2
Metals
_ZN ×4
Waters ×307
* Residue conservation analysis
PDB id:
1p0c
Name: Oxidoreductase
Title: Crystal structure of the NADP(h)-dependent vertebrate alcohol dehydrogenase (adh8)
Structure: NADP-dependent alcohol dehydrogenase. Chain: a, b. Engineered: yes
Source: Rana perezi. Perez's frog. Organism_taxid: 8403. Gene: adh. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.198     R-free:   0.234
Authors: A.Rosell,E.Valencia,X.Pares,I.Fita,J.Farres,W.F.Ochoa
Key ref:
A.Rosell et al. (2003). Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8). J Mol Biol, 330, 75-85. PubMed id: 12818203 DOI: 10.1016/S0022-2836(03)00431-5
Date:
10-Apr-03     Release date:   22-Apr-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
O57380  (ADH8_PELPE) -  NADP-dependent alcohol dehydrogenase from Pelophylax perezi
Seq:
Struc: 		373 a.a.
372 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: 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(+)
 = aldehyde
 + NADPH
 + H(+)
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/S0022-2836(03)00431-5 J Mol Biol 330:75-85 (2003)
PubMed id: 12818203  
 
 
Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8).
A.Rosell, E.Valencia, X.Parés, I.Fita, J.Farrés, W.F.Ochoa.
 
  ABSTRACT  
 
The amphibian enzyme ADH8, previously named class IV-like, is the only known vertebrate alcohol dehydrogenase (ADH) with specificity towards NADP(H). The three-dimensional structures of ADH8 and of the binary complex ADH8-NADP(+) have been now determined and refined to resolutions of 2.2A and 1.8A, respectively. The coenzyme and substrate specificity of ADH8, that has 50-65% sequence identity with vertebrate NAD(H)-dependent ADHs, suggest a role in aldehyde reduction probably as a retinal reductase. The large volume of the substrate-binding pocket can explain both the high catalytic efficiency of ADH8 with retinoids and the high K(m) value for ethanol. Preference of NADP(H) appears to be achieved by the presence in ADH8 of the triad Gly223-Thr224-His225 and the recruitment of conserved Lys228, which define a binding pocket for the terminal phosphate group of the cofactor. NADP(H) binds to ADH8 in an extended conformation that superimposes well with the NAD(H) molecules found in NAD(H)-dependent ADH complexes. No additional reshaping of the dinucleotide-binding site is observed which explains why NAD(H) can also be used as a cofactor by ADH8. The structural features support the classification of ADH8 as an independent ADH class.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Stereo views of the cofactor-binding pocket in the crystal structures of the (a) apo-ADH8 and of the (b) ADH8-NADP+ complex. Molecular models are represented by solid sticks with protein atoms colored according to their atom type. Bound phosphate and glycerol molecules, in the apo-ADH8 structure, and the NADP+ molecule, in the ADH8-NADP+ structure, are displayed in green. Electron densities, corresponding to the final 2F[o] -F[c] maps, are also shown, at 1s level, with a chicken box representation. 		Figure 4.
Figure 4. LIGPLOT[49.] describing interactions of the NADP+ molecule found in the structure of the ADH8-NADP+ complex. Only side-chains of residues Thr224, His225 and Lys228 interact with the terminal phosphate group of the NADP+ cofactor. Thr224 and His225 are sequence variations specific of ADH8 while Lys228 is conserved among NAD(H)-dependent ADHs (see in the text).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 330, 75-85) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19507198 M.Ehsani, M.R.Fernández, J.A.Biosca, and S.Dequin (2009).
Reversal of coenzyme specificity of 2,3-butanediol dehydrogenase from Saccharomyces cerevisae and in vivo functional analysis.
  Biotechnol Bioeng, 104, 381-389.  
19349281 S.Porté, E.Valencia, E.A.Yakovtseva, E.Borràs, N.Shafqat, J.E.Debreczeny, A.C.Pike, U.Oppermann, J.Farrés, I.Fita, and X.Parés (2009).
Three-dimensional Structure and Enzymatic Function of Proapoptotic Human p53-inducible Quinone Oxidoreductase PIG3.
  J Biol Chem, 284, 17194-17205.
PDB code: 2j8z
18632551 R.A.Harris, J.R.Trudell, and S.J.Mihic (2008).
Ethanol's molecular targets.
  Sci Signal, 1, re7.  
16358010 M.Domínguez, R.Alvarez, E.Borràs, J.Farrés, X.Parés, and A.R.de Lera (2006).
Synthesis of enantiopure C3- and C4-hydroxyretinals and their enzymatic reduction by ADH8 from Xenopus laevis.
  Org Biomol Chem, 4, 155-164.  
15995211 C.Montella, L.Bellsolell, R.Pérez-Luque, J.Badía, L.Baldoma, M.Coll, and J.Aguilar (2005).
Crystal structure of an iron-dependent group III dehydrogenase that interconverts L-lactaldehyde and L-1,2-propanediol in Escherichia coli.
  J Bacteriol, 187, 4957-4966.
PDB codes: 2bi4 2bl4
16121213 R.Gonzàlez-Duarte, and R.Albalat (2005).
Merging protein, gene and genomic data: the evolution of the MDR-ADH family.
  Heredity, 95, 184-197.  
15623532 S.Watanabe, T.Kodaki, and K.Makino (2005).
Complete reversal of coenzyme specificity of xylitol dehydrogenase and increase of thermostability by the introduction of structural zinc.
  J Biol Chem, 280, 10340-10349.  
12902331 A.Rosell, E.Valencia, W.F.Ochoa, I.Fita, X.Parés, and J.Farrés (2003).
Complete reversal of coenzyme specificity by concerted mutation of three consecutive residues in alcohol dehydrogenase.
  J Biol Chem, 278, 40573-40580.  
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.

 

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