Structural highlights
Function
[A9XG43_9ENTO] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[SAAS:SAAS000199_004_016611] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047]
Publication Abstract from PubMed
The crystal structure of 3C proteinase (3C(pro)) from Enterovirus 71 (EV71) was determined in space group C2221 to 2.2 A resolution. The fold was similar to that of 3C(pro) from other picornaviruses, but the difference in the beta-ribbon reported in a previous structure was not observed. This beta-ribbon was folded over the substrate-binding cleft and constituted part of the essential binding sites for interaction with the substrate. The structure of its complex with rupintrivir (AG7088), a peptidomimetic inhibitor, was also characterized in space group P212121 to 1.96 A resolution. The inhibitor was accommodated without any spatial hindrance despite the more constricted binding site; this was confirmed by functional assays, in which the inhibitor showed comparable potency towards EV71 3C(pro) and human rhinovirus 3C(pro), which is the target that rupintrivir was designed against.
Structures of Enterovirus 71 3C proteinase (strain E2004104-TW-CDC) and its complex with rupintrivir.,Wu C, Cai Q, Chen C, Li N, Peng X, Cai Y, Yin K, Chen X, Wang X, Zhang R, Liu L, Chen S, Li J, Lin T Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):866-71. doi:, 10.1107/S0907444913002862. Epub 2013 Apr 19. PMID:23633597[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu C, Cai Q, Chen C, Li N, Peng X, Cai Y, Yin K, Chen X, Wang X, Zhang R, Liu L, Chen S, Li J, Lin T. Structures of Enterovirus 71 3C proteinase (strain E2004104-TW-CDC) and its complex with rupintrivir. Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):866-71. doi:, 10.1107/S0907444913002862. Epub 2013 Apr 19. PMID:23633597 doi:10.1107/S0907444913002862
