title: 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.
authors.affiliation: Structural Biology Program, Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Lee
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Kuo
authors.forename: Min-Feng
authors.initials: MF
authors.lastname: Hsu
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Liang
authors.forename: Jim-Min
authors.initials: JM
authors.lastname: Fang
authors.forename: Jiun-Jie
authors.initials: JJ
authors.lastname: Shie
authors.forename: Andrew H-J
authors.initials: AH
authors.lastname: Wang
mesh_terms: D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases