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

doi:10.1016/j.febslet.2007.10.048

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

FEBS Lett. 2007 Nov 27;581(28):5454-8. doi: 10.1016/j.febslet.2007.10.048. Epub 2007 Nov 5.

Authors

Cheng-Chung Lee¹, Chih-Jung Kuo, Min-Feng Hsu, Po-Huang Liang, Jim-Min Fang, Jiun-Jie Shie, Andrew H-J Wang

Affiliation

¹ Structural Biology Program, Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Coronavirus 3C Proteases
Cysteine Endopeptidases / chemistry
Cysteine Endopeptidases / genetics
Cysteine Endopeptidases / metabolism
Models, Molecular
Molecular Structure
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Protein Binding
Severe acute respiratory syndrome-related coronavirus / enzymology*
Structure-Activity Relationship
Viral Proteins / antagonists & inhibitors*
Viral Proteins / chemistry
Viral Proteins / genetics
Viral Proteins / metabolism

Substances

Protease Inhibitors
Viral Proteins
Cysteine Endopeptidases
Coronavirus 3C Proteases