7ZVS

Crystal structure of the Schistosoma mansoni VKR2 kinase domain in an active-like state (ADP-bound)

7ZVS の概要

• エントリーDOI: 10.2210/pdb7zvs/pdb
• 分子名称: Venus kinase receptor 2, ADENOSINE-5'-DIPHOSPHATE (2 entities in total)
• 機能のキーワード: kinase, active-like state, transferase
• 由来する生物種: Schistosoma mansoni
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 117271.80

構造登録者

Beis, K.,Mathavan, I. (登録日: 2022-05-17, 公開日: 2022-10-12, 最終更新日: 2024-01-31)

主引用文献

Mathavan, I.,Liu, L.J.,Robinson, S.W.,El-Sakkary, N.,Elatico, A.J.J.,Gomez, D.,Nellas, R.,Owens, R.J.,Zuercher, W.,Navratilova, I.,Caffrey, C.R.,Beis, K.
Identification of Inhibitors of the Schistosoma mansoni VKR2 Kinase Domain.
Acs Med.Chem.Lett., 13:1715-1722, 2022

PubMed Abstract: Schistosomiasis is a neglected tropical disease caused by parasitic flatworms. Current treatment relies on just one partially effective drug, praziquantel (PZQ). Venus Kinase Receptors 1 and 2 (SmVKR1 and SmVKR2) are important for parasite growth and egg production, and are potential targets for combating schistosomiasis. VKRs consist of an extracellular Venus Flytrap Module (VFTM) linked via a transmembrane helix to a kinase domain. Here, we initiated a drug discovery effort to inhibit the activity of the SmVKR2 kinase domain (SmVKR2) by screening the GSK published kinase inhibitor set 2 (PKIS2). We identified several inhibitors, of which four were able to inhibit its enzymatic activity and induced phenotypic changes in . Our crystal structure of the SmVKR2 displays an active-like state that sheds light on the activation process of VKRs. Our data provide a basis for the further exploration of SmVKR2 as a possible drug target.

PubMed: 36385939
DOI: 10.1021/acsmedchemlett.2c00248

実験手法

X-RAY DIFFRACTION (3.07 Å)