2e99

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{{STRUCTURE_2e99| PDB=2e99 | SCENE= }}
{{STRUCTURE_2e99| PDB=2e99 | SCENE= }}
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'''E. coli undecaprenyl pyrophosphate synthase in complex with BPH-608'''
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===E. coli undecaprenyl pyrophosphate synthase in complex with BPH-608===
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==Overview==
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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 provide 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.
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{{ABSTRACT_PUBMED_17535895}}
==About this Structure==
==About this Structure==
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[[Category: Farnesyl pyrophosphate]]
[[Category: Farnesyl pyrophosphate]]
[[Category: Prenyltransferase]]
[[Category: Prenyltransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 02:10:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:48:20 2008''

Revision as of 11:48, 29 July 2008

Image:2e99.png

Template:STRUCTURE 2e99

E. coli undecaprenyl pyrophosphate synthase in complex with BPH-608

Template:ABSTRACT PUBMED 17535895

About this Structure

2E99 is a Single protein structure of sequence from Escherichia coli. 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 Jun 12;104(24):10022-7. Epub 2007 May 29. PMID:17535895

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