5CG5

Neutron crystal structure of human farnesyl pyrophosphate synthase in complex with risedronate

5CG5 の概要

• エントリーDOI: 10.2210/pdb5cg5/pdb
• 関連するPDBエントリー: 5cg6
• 分子名称: Farnesyl pyrophosphate synthase, MAGNESIUM ION, 1-HYDROXY-2-(3-PYRIDINYL)ETHYLIDENE BIS-PHOSPHONIC ACID, ... (4 entities in total)
• 機能のキーワード: prenyl transferase, bisphophonate, osteoprosis, inhibitor, transferase-transferase inhibotor complex, transferase/transferase inhibotor
• 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: 41386.88

構造登録者

Yokoyama, T.,Mizuguchi, M.,Ostermann, A.,Kusaka, K.,Niimura, N.,Schrader, T.E.,Tanaka, I. (登録日: 2015-07-09, 公開日: 2015-10-14, 最終更新日: 2024-04-03)

主引用文献

Yokoyama, T.,Mizuguchi, M.,Ostermann, A.,Kusaka, K.,Niimura, N.,Schrader, T.E.,Tanaka, I.
Protonation State and Hydration of Bisphosphonate Bound to Farnesyl Pyrophosphate Synthase
J.Med.Chem., 58:7549-7556, 2015

PubMed Abstract: Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate to FPP and is known to be a molecular target of osteoporosis drugs, such as risedronate (RIS), which is a nitrogen-containing bisphosphonate. The protonation states and hydration structure of RIS bound to FPPS were determined by neutron protein crystallography, which allows direct visualization of hydrogens and deuteriums. The structure analysis revealed that the phosphate groups of RIS were fully deprotonated with the abnormally decreased pKa, and that the roles of E93 and D264 consisted of canceling the extra negative charges upon the binding of ligands. Collectively, our neutron structures provided insights into the physicochemical properties during the bisphosphonate binding event.

PubMed: 26314394
DOI: 10.1021/acs.jmedchem.5b01147

実験手法

NEUTRON DIFFRACTION (2.4 Å)
X-RAY DIFFRACTION (1.402 Å)