4EA1

Co-crystal structure of dehydrosqualene synthase (Crtm) from S. aureus with SQ-109

4EA1 の概要

• エントリーDOI: 10.2210/pdb4ea1/pdb
• 関連するPDBエントリー: 4E9U 4E9Z 4EA0 4EA2
• 分子名称: Dehydrosqualene synthase, N-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-N'-[(1R,3S,5R,7R)-tricyclo[3.3.1.1~3,7~]dec-2-yl]ethane-1,2-diamine (3 entities in total)
• 機能のキーワード: prenyl transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34691.58

構造登録者

Lin, F.-Y.,Li, K.,Liu, Y.-L.,Oldfield, E. (登録日: 2012-03-21, 公開日: 2012-04-25, 最終更新日: 2024-02-28)

主引用文献

Lin, F.Y.,Liu, Y.L.,Li, K.,Cao, R.,Zhu, W.,Axelson, J.,Pang, R.,Oldfield, E.
Head-to-Head Prenyl Tranferases: Anti-Infective Drug Targets.
J.Med.Chem., 55:4367-4372, 2012

PubMed Abstract: We report X-ray crystallographic structures of three inhibitors bound to dehydrosqualene synthase from Staphylococcus aureus: 1 (BPH-651), 2 (WC-9), and 3 (SQ-109). Compound 2 binds to the S2 site with its -SCN group surrounded by four hydrogen bond donors. With 1, we report two structures: in both, the quinuclidine headgroup binds in the allylic (S1) site with the side chain in S2, but in the presence of PPi and Mg(2+), the quinuclidine's cationic center interacts with PPi and three Mg(2+), mimicking a transition state involved in diphosphate ionization. With 3, there are again two structures. In one, the geranyl side chain binds to either S1 or S2 and the adamantane headgroup binds to S1. In the second, the side chain binds to S2 while the headgroup binds to S1. These results provide structural clues for the mechanism and inhibition of the head-to-head prenyl transferases and should aid future drug design.

PubMed: 22486710
DOI: 10.1021/jm300208p

実験手法

X-RAY DIFFRACTION (2.46 Å)