2e8v
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(New page: 200px<br /><applet load="2e8v" size="350" color="white" frame="true" align="right" spinBox="true" caption="2e8v, resolution 1.80Å" /> '''S. cerevisiae gerany...)
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Revision as of 12:46, 23 January 2008
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S. cerevisiae geranylgeranyl pyrophosphate synthase in complex with product GGPP (P21)
Overview
Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act, primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in, decreased prenylation of small GTPases. Here, we show that some, bisphosphonates can also inhibit geranylgeranyl diphosphate synthase, (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a, cis-prenyltransferase of interest as a target for antibacterial therapy., Our results on GGPPS (10 structures) show that there are three, bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate, substrate-binding sites together with a GGPP product- or inhibitor-binding, site. In UPPS, there are a total of four binding sites (in five, structures). These results are of general interest because they provicd de, the first structures of GGPPS- and UPPS-inhibitor complexes, potentially, important drug targets, in addition to revealing a remarkably broad, spectrum of binding modes not seen in FPPS inhibition.
About this Structure
2E8V is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Active as Trans-hexaprenyltranstransferase, with EC number 2.5.1.30 Full crystallographic information is available from OCA.
Reference
Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases., Guo RT, Cao R, Liang PH, Ko TP, Chang TH, Hudock MP, Jeng WY, Chen CK, Zhang Y, Song Y, Kuo CJ, Yin F, Oldfield E, Wang AH, Proc Natl Acad Sci U S A. 2007 May 29;. PMID:17535895
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