3qzr

Publication Abstract from PubMed

EV71 is the primary pathogen causing HFMD, however, the effective antiviral drug is currently unavailable. Rupintrivir, an inhibitor against HRV, has potent antiviral activities against EV71. We determined high-resolution crystal structures of EV71 3C(pro)/rupintrivir complex, showing that although rupintrivir interacts with EV71 3C(pro) similarly as with HRV 3C(pro), the C-terminal of the inhibitor cannot accommodate in the leaving group pockets of EV71 3C(pro). Our structures reveal that EV71 3C(pro) possesses a surface-recessive S2' pocket that is not present in HRV 3C(pro), which contribute to the additional substrate binding affinity. Combined with mutagenic studies, we demonstrated that the catalytic Glu71 is irreplaceable for maintaining the overall architecture of the active site and most importantly, the productive conformation of the catalytic His40. We discovered the role of a previously uncharacterized residue Arg39 of EV71 3C(pro) that can neutralize the negative charge of Glu71, which may subsequently assists the deprotonation of His40 during the proteolysis.

Crystal Structures of Enterovirus 71 3C Protease Complexed with Rupintrivir Reveal the Roles of the Catalytically Important Residues.,Wang J, Fan T, Yao X, Wu Z, Guo L, Lei X, Wang J, Wang M, Jin Q, Cui S J Virol. 2011 Aug 3. PMID:21813612^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.