3BPM

Crystal Structure of Falcipain-3 with Its inhibitor, Leupeptin

3BPM の概要

• エントリーDOI: 10.2210/pdb3bpm/pdb
• 関連するPDBエントリー: 1AIM 1YVB 2GHU 3BPF
• 関連するBIRD辞書のPRD_ID: PRD_000216
• 分子名称: Cysteine protease falcipain-3, Leupeptin, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: falcipain, malaria, cysteine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Plasmodium falciparum; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 56090.63

構造登録者

kerr, I.D.,Lee, J.H.,Brinen, L.S. (登録日: 2007-12-18, 公開日: 2008-12-30, 最終更新日: 2024-11-20)

主引用文献

Kerr, I.D.,Lee, J.H.,Pandey, K.C.,Harrison, A.,Sajid, M.,Rosenthal, P.J.,Brinen, L.S.
Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.
J.Med.Chem., 52:852-857, 2009

PubMed Abstract: Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes.

PubMed: 19128015
DOI: 10.1021/jm8013663

実験手法

X-RAY DIFFRACTION (2.5 Å)