5T6D

2.10 A resolution structure of Norovirus 3CL protease in complex with the dipeptidyl inhibitor 7l (hexagonal form)

5T6D の概要

• エントリーDOI: 10.2210/pdb5t6d/pdb
• 関連するPDBエントリー: 5T6F 5T6G
• 分子名称: Genome polyprotein, 3-cyclohexyl-N-{(2S)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-N~2~-{[3-(4-methoxyphenoxy)propyl]sulfonyl}-L- alaninamide (3 entities in total)
• 機能のキーワード: protease, norovirus, norwalk virus, antiviral inhibitors, dipeptidyl inhibitor, protease-protease inhibitor complex, protease/protease inhibitor
• 由来する生物種: Norwalk virus (Hu/NV/NV/1968/US)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41331.63

構造登録者

Lovell, S.,Battaile, K.P.,Mehzabeen, N.,Kankanamalage, A.C.G.,Kim, Y.,Rathnayake, A.D.,Damalanka, V.C.,Weerawarna, P.M.,Doyle, S.T.,Alsoudi, A.F.,Dissanayake, D.M.P.,Chang, K.-O.,Groutas, W.C. (登録日: 2016-09-01, 公開日: 2016-11-23, 最終更新日: 2024-11-20)

主引用文献

Galasiti Kankanamalage, A.C.,Kim, Y.,Rathnayake, A.D.,Damalanka, V.C.,Weerawarna, P.M.,Doyle, S.T.,Alsoudi, A.F.,Dissanayake, D.M.,Lushington, G.H.,Mehzabeen, N.,Battaile, K.P.,Lovell, S.,Chang, K.O.,Groutas, W.C.
Structure-based exploration and exploitation of the S4 subsite of norovirus 3CL protease in the design of potent and permeable inhibitors.
Eur J Med Chem, 126:502-516, 2016

PubMed Abstract: Human noroviruses are the primary cause of epidemic and sporadic acute gastroenteritis. The worldwide high morbidity and mortality associated with norovirus infections, particularly among the elderly, immunocompromised patients and children, constitute a serious public health concern. There are currently no approved human vaccines or norovirus-specific small-molecule therapeutics or prophylactics. Norovirus 3CL protease has recently emerged as a potential therapeutic target for the development of anti-norovirus agents. We hypothesized that the S subsite of the enzyme may provide an effective means of designing potent and cell permeable inhibitors of the enzyme. We report herein the structure-guided exploration and exploitation of the S subsite of norovirus 3CL protease in the design and synthesis of effective inhibitors of the protease.

PubMed: 27914364
DOI: 10.1016/j.ejmech.2016.11.027

実験手法

X-RAY DIFFRACTION (2.1 Å)