7ZVS
Crystal structure of the Schistosoma mansoni VKR2 kinase domain in an active-like state (ADP-bound)
Summary for 7ZVS
| Entry DOI | 10.2210/pdb7zvs/pdb |
| Descriptor | Venus kinase receptor 2, ADENOSINE-5'-DIPHOSPHATE (2 entities in total) |
| Functional Keywords | kinase, active-like state, transferase |
| Biological source | Schistosoma mansoni |
| Total number of polymer chains | 3 |
| Total formula weight | 117271.80 |
| Authors | Beis, K.,Mathavan, I. (deposition date: 2022-05-17, release date: 2022-10-12, Last modification date: 2024-01-31) |
| Primary citation | 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 Cited by 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: 36385939DOI: 10.1021/acsmedchemlett.2c00248 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.07 Å) |
Structure validation
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