5HNA

Crystal structure of Plasmodium vivax geranylgeranylpyrophosphate synthase complexed with BPH-1251

5HNA の概要

• エントリーDOI: 10.2210/pdb5hna/pdb
• 関連するPDBエントリー: 5HN7 5HN8 5HN9
• 分子名称: Farnesyl pyrophosphate synthase, putative, 4-chloro-2-{[3-(decyloxy)-5-hydroxybenzyl]oxy}-5-sulfamoylbenzoic acid (3 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: Plasmodium vivax
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 177192.88

構造登録者

Liu, Y.-L.,Zhang, Y.,Oldfield, E. (登録日: 2016-01-18, 公開日: 2016-09-07, 最終更新日: 2023-09-27)

主引用文献

G Ricci, C.,Liu, Y.L.,Zhang, Y.,Wang, Y.,Zhu, W.,Oldfield, E.,McCammon, J.A.
Dynamic Structure and Inhibition of a Malaria Drug Target: Geranylgeranyl Diphosphate Synthase.
Biochemistry, 55:5180-5190, 2016

PubMed Abstract: We report a molecular dynamics investigation of the structure, function, and inhibition of geranylgeranyl diphosphate synthase (GGPPS), a potential drug target, from the malaria parasite Plasmodium vivax. We discovered several GGPPS inhibitors, benzoic acids, and determined their structures crystallographically. We then used molecular dynamics simulations to investigate the dynamics of three such inhibitors and two bisphosphonate inhibitors, zoledronate and a lipophilic analogue of zoledronate, as well as the enzyme's product, GGPP. We were able to identify the main motions that govern substrate binding and product release as well as the molecular features required for GGPPS inhibition by both classes of inhibitor. The results are of broad general interest because they represent the first detailed investigation of the mechanism of action, and inhibition, of an important antimalarial drug target, geranylgeranyl diphosphate synthase, and may help guide the development of other, novel inhibitors as new drug leads.

PubMed: 27564465
DOI: 10.1021/acs.biochem.6b00398

実験手法

X-RAY DIFFRACTION (2.693 Å)