3sgt | pdb_00003sgt

Crystal Structure of E. coli undecaprenyl pyrophosphate synthase in complex with BPH-1299

spinqualitylabelsall models 3sgt, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3sgt is a 2 chain structure with sequence from Escherichia coli o6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: P09 Gene: uppS, c0211 (Escherichia coli O6) Activity: Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl- diphosphate specific), with EC number 2.5.1.31 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [UPPS_ECOL6] Catalyzes the sequential condensation of isopentenyl diphosphate (IPP) with (2E,6E)-farnesyl diphosphate (E,E-FPP) to yield (2Z,6Z,10Z,14Z,18Z,22Z,26Z,30Z,34E,38E)-undecaprenyl diphosphate (di-trans,octa-cis-UPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide.[HAMAP-Rule:MF_01139] Publication Abstract from PubMed With the rise in resistance to antibiotics such as methicillin, there is a need for new drugs. We report here the discovery and X-ray crystallographic structures of 10 chemically diverse compounds (benzoic, diketo, and phosphonic acids, as well as a bisamidine and a bisamine) that inhibit bacterial undecaprenyl diphosphate synthase, an essential enzyme involved in cell wall biosynthesis. The inhibitors bind to one or more of the four undecaprenyl diphosphate synthase inhibitor binding sites identified previously, with the most active leads binding to site 4, outside the catalytic center. The most potent leads are active against Staphylococcus aureus [minimal inhibitory concentration (MIC)(90) approximately 0.25 microg/mL], and one potently synergizes with methicillin (fractional inhibitory concentration index = 0.25) and is protective in a mouse infection model. These results provide numerous leads for antibacterial development and open up the possibility of restoring sensitivity to drugs such as methicillin, using combination therapies. Antibacterial drug leads targeting isoprenoid biosynthesis.,Zhu W, Zhang Y, Sinko W, Hensler ME, Olson J, Molohon KJ, Lindert S, Cao R, Li K, Wang K, Wang Y, Liu YL, Sankovsky A, de Oliveira CA, Mitchell DA, Nizet V, McCammon JA, Oldfield E Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):123-8. doi: 10.1073/pnas.1219899110. , Epub 2012 Dec 17. PMID:23248302 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Undecaprenyl pyrophosphate synthase

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