Structural basis of mercury‐ and zinc‐conjugated complexes as SARS‐CoV 3C‐like protease inhibitors

Five active metal‐conjugated inhibitors (PMA, TDT, EPDTC, JMF1586 and JMF1600) bound with the 3C‐like protease of severe acute respiratory syndrome (SARS)‐associated coronavirus were analyzed crystallographically. The complex structures reveal two major inhibition modes: Hg(2+)‐PMA is coordinated to...

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Detalles Bibliográficos
Autores principales: Lee, Cheng-Chung, Kuo, Chih-Jung, Hsu, Min-Feng, Liang, Po-Huang, Fang, Jim-Min, Shie, Jiun-Jie, Wang, Andrew H.-J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2007
Materias:
Short Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094272/
https://www.ncbi.nlm.nih.gov/pubmed/17981158
http://dx.doi.org/10.1016/j.febslet.2007.10.048
Descripción
Sumario:Five active metal‐conjugated inhibitors (PMA, TDT, EPDTC, JMF1586 and JMF1600) bound with the 3C‐like protease of severe acute respiratory syndrome (SARS)‐associated coronavirus were analyzed crystallographically. The complex structures reveal two major inhibition modes: Hg(2+)‐PMA is coordinated to C(44), M(49) and Y(54) with a square planar geometry at the S3 pocket, whereas each Zn(2+) of the four zinc‐inhibitors is tetrahedrally coordinated to the H(41)–C(145) catalytic dyad. For anti‐SARS drug design, this Zn(2+)‐centered coordination pattern would serve as a starting platform for inhibitor optimization.

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