5h9d

Crystal structure of Heptaprenyl Diphosphate Synthase from Staphylococcus aureus

spinqualitylabelsall models 5h9d, resolution 2.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5h9d is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We report the first structure of heptaprenyl diphosphate synthase from Staphylococcus aureus (SaHepPPS), together with an investigation of its mechanism of action and inhibition. The protein is involved in the formation of menaquinone, a key electron transporter in many bacteria, including pathogens. SaHepPPS consists of a "catalytic " subunit (SaHepPPS-2) having two "DDXXD" motifs and a "regulatory" subunit (SaHepPPS-1) that lacks these motifs. High concentrations of the substrates, isopentenyl diphosphate and farnesyl diphosphate, inhibit the enzyme, which is also potently inhibited by bisphosphonates. The most active inhibitors (Ki approximately 200 nm) were N-alkyl analogues of zoledronate containing approximately C6 alkyl side chains. They were modestly active against S. aureus cell growth, and growth inhibition was partially "rescued" by the addition of menaquinone-7. Because SaHepPPS is essential for S. aureus cell growth, its structure is of interest in the context of the development of menaquinone biosynthesis inhibitors as potential antibiotic leads. Structure, Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase.,Desai J, Liu YL, Wei H, Liu W, Ko TP, Guo RT, Oldfield E ChemMedChem. 2016 Sep 6;11(17):1915-23. doi: 10.1002/cmdc.201600311. Epub 2016, Jul 26. PMID:27457559 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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