4QXS

Crystal structure of human FPPS in complex with WC01088

4QXS の概要

• エントリーDOI: 10.2210/pdb4qxs/pdb
• 分子名称: Farnesyl pyrophosphate synthase, PHOSPHATE ION, (2-{2-[(2S)-3-methylbutan-2-yl]-5-phenyl-1H-indol-3-yl}ethane-1,1-diyl)bis(phosphonic acid), ... (5 entities in total)
• 機能のキーワード: 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: 43878.41

構造登録者

Park, J.,Zielinski, M.,Weiling, C.,Tsantrizos, Y.S.,Berghuis, A.M. (登録日: 2014-07-21, 公開日: 2015-02-25, 最終更新日: 2023-09-20)

主引用文献

Gritzalis, D.,Park, J.,Chiu, W.,Cho, H.,Lin, Y.S.,De Schutter, J.W.,Lacbay, C.M.,Zielinski, M.,Berghuis, A.M.,Tsantrizos, Y.S.
Probing the molecular and structural elements of ligands binding to the active site versus an allosteric pocket of the human farnesyl pyrophosphate synthase.
Bioorg.Med.Chem.Lett., 25:1117-1123, 2015

PubMed Abstract: In order to explore the interactions of bisphosphonate ligands with the active site and an allosteric pocket of the human farnesyl pyrophosphate synthase (hFPPS), substituted indole and azabenzimidazole bisphosphonates were designed as chameleon ligands. NMR and crystallographic studies revealed that these compounds can occupy both sub-pockets of the active site cavity, as well as the allosteric pocket of hFPPS in the presence of the enzyme's Mg(2+) ion cofactor. These results are consistent with the previously proposed hypothesis that the allosteric pocket of hFPPS, located near the active site, plays a feed-back regulatory role for this enzyme.

PubMed: 25630225
DOI: 10.1016/j.bmcl.2014.12.089

実験手法

X-RAY DIFFRACTION (1.9 Å)