4H5C

Crystal structure of human FPPS in ternary complex with YS0470 and inorganic phosphate

4H5C の概要

• エントリーDOI: 10.2210/pdb4h5c/pdb
• 関連するPDBエントリー: 4DEM 4H5D 4H5E
• 分子名称: Farnesyl pyrophosphate synthase, [({4-[4-(propan-2-yloxy)phenyl]pyridin-2-yl}amino)methanediyl]bis(phosphonic acid), PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P14324
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43715.14

構造登録者

Park, J.,Lin, Y.-S.,Tsantrizos, Y.S.,Berghuis, A.M. (登録日: 2012-09-18, 公開日: 2012-12-26, 最終更新日: 2023-09-20)

主引用文献

Park, J.,Lin, Y.S.,De Schutter, J.W.,Tsantrizos, Y.S.,Berghuis, A.M.
Ternary complex structures of human farnesyl pyrophosphate synthase bound with a novel inhibitor and secondary ligands provide insights into the molecular details of the enzyme's active site closure.
Bmc Struct.Biol., 12:32-32, 2012

PubMed Abstract: Human farnesyl pyrophosphate synthase (FPPS) controls intracellular levels of farnesyl pyrophosphate, which is essential for various biological processes. Bisphosphonate inhibitors of human FPPS are valuable therapeutics for the treatment of bone-resorption disorders and have also demonstrated efficacy in multiple tumor types. Inhibition of human FPPS by bisphosphonates in vivo is thought to involve closing of the enzyme's C-terminal tail induced by the binding of the second substrate isopentenyl pyrophosphate (IPP). This conformational change, which occurs through a yet unclear mechanism, seals off the enzyme's active site from the solvent environment and is essential for catalysis. The crystal structure of human FPPS in complex with a novel bisphosphonate YS0470 and in the absence of a second substrate showed partial ordering of the tail in the closed conformation.

PubMed: 23234314
DOI: 10.1186/1472-6807-12-32

実験手法

X-RAY DIFFRACTION (2.02 Å)