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
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- 作者：Maria K. Tsoumpraa ; b ; 1 ; Joao R. Munizb ; 2 ; Bobby L. Barnettc ; Aaron A. Kwaasia ; Ewa S. Pilkab ; 3 ; Kathryn L. Kavanaghb ; 4 ; Artem Evdokimovf ; Richard L. Walterg ; Frank Von Delftb ; Frank H. Ebetinob ; d ; Udo Oppermanna ; b ; R. Graham G. Russella ; e ; James E. Dunforda ; b ; james.dunford@ndorms.ox.ac.uk" class="auth_mail" title="E-mail the corresponding author
- 关键词：DMAPP ; dimethylallyl pyrophosphate ; FPP ; farnesyl pyrophosphate ; FPPS ; farnesyl pyrophosphate synthase ; GPP ; geranyl pyrophosphate ; IPP ; isopentenyl pyrophosphate ; N-BP ; nitrogen-containing bisphosphonates ; TCEP ; tris(2-carboxyethyl)phosphine ; RIS ; Risedronate ; ZOL ; Zoledronate ; PAM ; Pamidronate ; ALN ; Alendronate ; IBN ; Ibandronate
- 刊名：Bone
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：81
- 期：Complete
- 页码：478-486
- 全文大小：993 K
文摘
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Bisphosphonate side chain nitrogen interaction with side chain of Thr201 is essential for maximal inhibition by ZOL
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Tyr204 is essential for maximal inhibition by RIS but not aminoalkyl bisphosphonates
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Active site residues Thr201 and Tyr204 aid formation of the second substrate IPP binding site