PDBsum entry 1tve

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Oxidoreductase PDB id
Protein chains
358 a.a. *
178 ×2
* Residue conservation analysis
PDB id:
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)
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
29-Jun-04     Release date:   13-Jul-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P31116  (DHOM_YEAST) -  Homoserine dehydrogenase
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.
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.  
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