4h8e

Structure of S. aureus undecaprenyl diphosphate synthase in complex with FPP and sulfate

spinqualitylabelsall models 4h8e, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4h8e is a 1 chain structure with sequence from Staphylococcus aureus subsp. aureus N315. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FPP, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ISPT_STAAN Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[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

Proteopedia Page Contributors and Editors (what is this?)

OCA