2f94: Difference between revisions

Revision as of 05:53, 28 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:2f94.png

Template:STRUCTURE 2f94

Crystal structure of human FPPS in complex with ibandronateCrystal structure of human FPPS in complex with ibandronate

Template:ABSTRACT PUBMED 16892359

About this StructureAbout this Structure

2F94 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs., Rondeau JM, Bitsch F, Bourgier E, Geiser M, Hemmig R, Kroemer M, Lehmann S, Ramage P, Rieffel S, Strauss A, Green JR, Jahnke W, ChemMedChem. 2006 Feb;1(2):267-73. PMID:16892359

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Crystal structure of human FPPS in complex with ibandronate'''
+===Crystal structure of human FPPS in complex with ibandronate===
-==Overview==
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-To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). By revealing three structural snapshots of the enzyme catalytic cycle, each associated with a distinct conformational state, and details about the interactions with N-BPs, these structures provide a novel understanding of the mechanism of FPPS catalysis and inhibition. In particular, the accumulating substrate, IPP, was found to bind to and stabilize the FPPS-N-BP complexes rather than to compete with and displace the N-BP inhibitor. Stabilization of the FPPS-N-BP complex through IPP binding is supported by differential scanning calorimetry analyses of a set of representative N-BPs. Among other factors such as high binding affinity for bone mineral, this particular mode of FPPS inhibition contributes to the exceptional in vivo efficacy of N-BP drugs. Moreover, our data form the basis for structure-guided design of optimized N-BPs with improved pharmacological properties.
+The line below this paragraph, {{ABSTRACT_PUBMED_16892359}}, adds the Publication Abstract to the page
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+{{ABSTRACT_PUBMED_16892359}}
 ==About this Structure==
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 [[Category: Isoprene biosynthesis]]
 [[Category: Mevalonate pathway]]
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