4f6x | pdb_00004f6x

Crystal structure of dehydrosqualene synthase (crtm) from s. aureus complexed with bph-1112

spinqualitylabelsall models 4f6x, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4f6x is a 1 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, TAR, ZYL Gene: crtM ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885) Activity: 4,4'-diapophytoene synthase, with EC number 2.5.1.96 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We report the discovery of antibacterial leads, keto- and diketo-acids, targeting two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and dehydrosqualene synthase (CrtM). The leads were suggested by the observation that keto- and diketo-acids bind to the active site Mg(2+)/Asp domain in HIV-1 integrase, and similar domains are present in prenyl transferases. We report the x-ray crystallographic structures of one diketo-acid and one keto-acid bound to CrtM, which supports the Mg(2+) binding hypothesis, together with the x-ray structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth inhibition MIC(90) values of ~250-500 ng/mL against S. aureus, 500 ng/mL against Bacillus anthracis, 4 mug/mL against Listeria monocytogenes and Enterococcus faecium, and 1 mug/mL against Streptococcus pyogenes M1, but very little activity against E. coli (DH5alpha, K12) or human cell lines. HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid Biosynthesis.,Zhang Y, Fu-Yang Lin, Li K, Zhu W, Liu YL, Cao R, Pang R, Lee E, Axelson J, Hensler M, Wang K, Molohon KJ, Wang Y, Mitchell DA, Nizet V, Oldfield E ACS Med Chem Lett. 2012 Apr 3;3(5):402-406. PMID:22662288 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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