2xpc

Second-generation sulfonamide inhibitors of MurD: Activity optimisation with conformationally rigid analogues of D-glutamic acidSecond-generation sulfonamide inhibitors of MurD: Activity optimisation with conformationally rigid analogues of D-glutamic acid

Structural highlights 2xpc is a 1 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , NonStd Res: Activity: UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase, with EC number 6.3.2.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MURD_ECO57] Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA). Publication Abstract from PubMed d-Glutamic acid-adding enzyme (MurD) catalyses the essential addition of d-glutamic acid to the cytoplasmic peptidoglycan precursor UDP-N-acetylmuramoyl-l-alanine, and as such it represents an important antibacterial drug-discovery target enzyme. Based on a series of naphthalene-N-sulfonyl-d-Glu derivatives synthesised recently, we synthesised two series of new, optimised sulfonamide inhibitors of MurD that incorporate rigidified mimetics of d-Glu. The compounds that contained either constrained d-Glu or related rigid d-Glu mimetics showed significantly better inhibitory activities than the parent compounds, thereby confirming the advantage of molecular rigidisation in the design of MurD inhibitors. The binding modes of the best inhibitors were examined with high-resolution NMR spectroscopy and X-ray crystallography. We have solved a new crystal structure of the complex of MurD with an inhibitor bearing a 4-aminocyclohexane-1,3-dicarboxyl moiety. These data provide an additional step towards the development of sulfonamide inhibitors with potential antibacterial activities. Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of d-glutamic acid.,Sosic I, Barreteau H, Simcic M, Sink R, Cesar J, Zega A, Grdadolnik SG, Contreras-Martel C, Dessen A, Amoroso A, Joris B, Blanot D, Gobec S Eur J Med Chem. 2011 Apr 9. PMID:21524830 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mur ligase

spinqualitylabelsall models 2xpc, resolution 1.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image