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

Cheng Chung Lee, Chih Jung Kuo, Min Feng Hsu, Po Huang Liang, Jim Min Fang, Jiun Jie Shie, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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: Hg2+-PMA is coordinated to C44, M49 and Y54 with a square planar geometry at the S3 pocket, whereas each Zn2+ of the four zinc-inhibitors is tetrahedrally coordinated to the H41-C145 catalytic dyad. For anti-SARS drug design, this Zn2+-centered coordination pattern would serve as a starting platform for inhibitor optimization.

Original languageEnglish
Pages (from-to)5454-5458
Number of pages5
JournalFEBS Letters
Volume581
Issue number28
DOIs
Publication statusPublished - Nov 27 2007
Externally publishedYes

Keywords

  • Metal ion
  • Protease inhibitor
  • SARS

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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