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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/Q2FYG6_STAA8 Q2FYG6_STAA8] | | [https://www.uniprot.org/uniprot/Q2FYG6_STAA8 Q2FYG6_STAA8] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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<ref>PMID:27457559</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 5h9d" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |