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The inhibition of human farnesyl pyrophosphate synthase by nitrogen-containing bisphosphonates. Elucidating the role of active site threonine 201 and tyrosine 204 residues using enzyme mutants.

Abstract:

Farnesyl pyrophosphate synthase (FPPS) is the major molecular target of nitrogen-containing bisphosphonates (N-BPs), used clinically as bone resorption inhibitors. We investigated the role of threonine 201 (Thr201) and tyrosine 204 (Tyr204) residues in substrate binding, catalysis and inhibition by N-BPs, employing kinetic and crystallographic studies of mutated FPPS proteins. Mutants of Thr201 illustrated the importance of the methyl group in aiding the formation of the Isopentenyl pyrophosp...

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Publisher copy:
10.1016/j.bone.2015.08.020

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Journal:
Bone
Volume:
81
Pages:
478-486
Chapter number:
C
Publication date:
2015-08-28
DOI:
EISSN:
1873-2763
ISSN:
8756-3282
URN:
uuid:a104ae36-de74-4760-ae0f-81c0a3d5ed98
Source identifiers:
541559
Local pid:
pubs:541559

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