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PDBsum entry 1tve

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1tve
Jmol
Contents
Protein chains
358 a.a. *
Ligands
178 ×2
* Residue conservation analysis
PDB id:
1tve
Name: Oxidoreductase
Title: Homoserine dehydrogenase in complex with 4-(4-hydroxy-3- isopropylphenylthio)-2-isopropylphenol
Structure: Homoserine dehydrogenase. Chain: a, b. Synonym: hdh. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: hom6. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.289     R-free:   0.363
Authors: L.Ejim,I.A.Mirza,C.Capone,I.Nazi,S.Jenkins,G.L.Chee, A.M.Berghuis,G.D.Wright
Key ref: L.Ejim et al. (2004). New phenolic inhibitors of yeast homoserine dehydrogenase. Bioorg Med Chem, 12, 3825-3830. PubMed id: 15210149 DOI: 10.1016/j.bmc.2004.05.009
Date:
29-Jun-04     Release date:   13-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P31116  (DHOM_YEAST) -  Homoserine dehydrogenase
Seq:
Struc:
359 a.a.
358 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   8 terms 
  Biochemical function     oxidoreductase activity     3 terms  

 

 
DOI no: 10.1016/j.bmc.2004.05.009 Bioorg Med Chem 12:3825-3830 (2004)
PubMed id: 15210149  
 
 
New phenolic inhibitors of yeast homoserine dehydrogenase.
L.Ejim, I.A.Mirza, C.Capone, I.Nazi, S.Jenkins, G.L.Chee, A.M.Berghuis, G.D.Wright.
 
  ABSTRACT  
 
A relatively unexploited potential target for antimicrobial agents is the biosynthesis of essential amino acids. Homoserine dehydrogenase, which reduces aspartate semi-aldehyde to homoserine in a NAD(P)H-dependent reaction, is one such target that is required for the biosynthesis of Met, Thr, and Ile from Asp. We report a small molecule screen of yeast homoserine dehydrogenase that has identified a new class of phenolic inhibitors of this class of enzyme. X-ray crystal structural analysis of one of the inhibitors in complex with homoserine dehydrogenase reveals that these molecules bind in the amino acid binding region of the active site and that the phenolic hydroxyl group interacts specifically with the backbone amide of Gly175. These results provide the first nonamino acid inhibitors of this class of enzyme and have the potential to be exploited as leads in antifungal compound design.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20305002 J.M.Kingsbury, and J.H.McCusker (2010).
Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1Delta) mutants.
  Eukaryot Cell, 9, 717-728.  
18216013 C.Zubieta, K.A.Arkus, R.E.Cahoon, and J.M.Jez (2008).
A single amino acid change is responsible for evolution of acyltransferase specificity in bacterial methionine biosynthesis.
  J Biol Chem, 283, 7561-7567.
PDB code: 2vdj
17353245 I.Nazi, A.Scott, A.Sham, L.Rossi, P.R.Williamson, J.W.Kronstad, and G.D.Wright (2007).
Role of homoserine transacetylase as a new target for antifungal agents.
  Antimicrob Agents Chemother, 51, 1731-1736.  
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.