1rqi

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{{STRUCTURE_1rqi| PDB=1rqi | SCENE= }}
{{STRUCTURE_1rqi| PDB=1rqi | SCENE= }}
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'''Active Conformation of Farnesyl Pyrophosphate Synthase Bound to Isopentyl Pyrophosphate and Dimethylallyl S-Thiolodiphosphate'''
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===Active Conformation of Farnesyl Pyrophosphate Synthase Bound to Isopentyl Pyrophosphate and Dimethylallyl S-Thiolodiphosphate===
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==Overview==
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Farnesyl pyrophosphate synthetase (FPPS) synthesizes farnesyl pyrophosphate through successive condensations of isopentyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs used to treat osteoclast-mediated bone resorption and tumor-induced hypercalcemia are potent inhibitors of the enzyme. Here we present crystal structures of substrate and bisphosphonate complexes of FPPS. The structures reveal how enzyme conformational changes organize conserved active site residues to exploit metal-induced ionization and substrate positioning for catalysis. The structures further demonstrate how nitrogen-containing bisphosphonates mimic a carbocation intermediate to inhibit the enzyme. Together, these FPPS complexes provide a structural template for the design of novel inhibitors that may prove useful for the treatment of osteoporosis and other clinical indications including cancer.
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(as it appears on PubMed at http://www.pubmed.gov), where 14672944 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14672944}}
==About this Structure==
==About this Structure==
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[[Category: Zhang, Y.]]
[[Category: Zhang, Y.]]
[[Category: Isoprenyl synthase]]
[[Category: Isoprenyl synthase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:47:38 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:15:48 2008''

Revision as of 13:15, 27 July 2008

Image:1rqi.png

Template:STRUCTURE 1rqi

Active Conformation of Farnesyl Pyrophosphate Synthase Bound to Isopentyl Pyrophosphate and Dimethylallyl S-Thiolodiphosphate

Template:ABSTRACT PUBMED 14672944

About this Structure

1RQI is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis., Hosfield DJ, Zhang Y, Dougan DR, Broun A, Tari LW, Swanson RV, Finn J, J Biol Chem. 2004 Mar 5;279(10):8526-9. Epub 2003 Dec 12. PMID:14672944

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