1rtr
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(New page: 200px<br /><applet load="1rtr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rtr, resolution 2.50Å" /> '''Crystal Structure of...)
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Revision as of 21:06, 24 November 2007
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Crystal Structure of S. Aureus Farnesyl Pyrophosphate Synthase
Overview
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.
About this Structure
1RTR is a Single protein structure of sequence from Staphylococcus aureus. 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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