4PI3

Crystal structure analysis of cruzain bound to vinyl sulfone analog of WRR-483 (WRR-666)

4PI3 の概要

• エントリーDOI: 10.2210/pdb4pi3/pdb
• 関連するPDBエントリー: 2OZ2 3LXS 4XUI
• 分子名称: Cruzipain, N-[(2S)-5-(carbamimidamidooxy)-1-oxo-1-{[(1E,3S)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]amino}pentan-2-yl]-4-methylpiperazine-1-carboxamide (3 entities in total)
• 機能のキーワード: cystein protease, cruzain, chagas disease, covalent inhibitor, vinyl sulfone derivative, analoge of wrr-483, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Trypanosoma cruzi
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46743.86

構造登録者

Tochowicz, A.,McKerrow, J.H. (登録日: 2014-05-08, 公開日: 2014-11-12, 最終更新日: 2024-10-16)

主引用文献

Jones, B.D.,Tochowicz, A.,Tang, Y.,Cameron, M.D.,McCall, L.I.,Hirata, K.,Siqueira-Neto, J.L.,Reed, S.L.,McKerrow, J.H.,Roush, W.R.
Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain.
Acs Med.Chem.Lett., 7:77-82, 2016

PubMed Abstract: A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cruzain inhibitors. Co-crystal structures of the oxyguanidine analogues WRR-666 (4) and WRR-669 (7) bound to cruzain demonstrated different binding interactions with the cysteine protease, depending on the aryl moiety of the P1' inhibitor subunit. Specifically, these data demonstrate that WRR-669 is bound noncovalently in the crystal structure. This represents a rare example of noncovalent inhibition of a cysteine protease by a vinyl sulfone inhibitor.

PubMed: 26819670
DOI: 10.1021/acsmedchemlett.5b00336

実験手法

X-RAY DIFFRACTION (1.27 Å)