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

ABSTRACT: 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.

SUBMITTER: Lee CC

PROVIDER: S-EPMC7094272 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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

Lee Cheng-Chung CC Kuo Chih-Jung CJ Hsu Min-Feng MF Liang Po-Huang PH Fang Jim-Min JM Shie Jiun-Jie JJ Wang Andrew H-J AH

FEBS letters 20071105 28

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 d ...[more]

PMID: 17981158

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