Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The inhibition of cysteine biosynthesis in prokaryotes and protozoa has been proposed to be relevant for the development of antibiotics. Haemophilus influenzae O-acetylserine sulfhydrylase (OASS), catalyzing l-cysteine formation, is inhibited by the insertion of the C-terminal pentapeptide (MNLNI) of serine acetyltransferase into the active site. Four-hundred MNXXI pentapeptides were generated in silico, docked into OASS active site using GOLD, and scored with HINT. The terminal P5 Ile accounts for about 50% of the binding energy. Glu or Asp at position P4 and, to a lesser extent, at position P3 also significantly contribute to the binding interaction. The predicted affinity of 14 selected pentapeptides correlated well with the experimentally determined dissociation constants. The X-ray structure of three high affinity pentapeptide-OASS complexes were compared with the docked poses. These results, combined with a GRID analysis of the active site, allowed us to define a pharmacophoric scaffold for the design of peptidomimetic inhibitors.
Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature.,Salsi E, Bayden AS, Spyrakis F, Amadasi A, Campanini B, Bettati S, Dodatko T, Cozzini P, Kellogg GE, Cook PF, Roderick SL, Mozzarelli A J Med Chem. 2010 Jan 14;53(1):345-56. PMID:19928859[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Salsi E, Bayden AS, Spyrakis F, Amadasi A, Campanini B, Bettati S, Dodatko T, Cozzini P, Kellogg GE, Cook PF, Roderick SL, Mozzarelli A. Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature. J Med Chem. 2010 Jan 14;53(1):345-56. PMID:19928859 doi:10.1021/jm901325e
