4fvd

Publication Abstract from PubMed

2A proteinase (2Apro) is an enterovirally encoded cysteine protease that plays essential roles in both the processing of viral precursor polyprotein and the hijack of host cell translation and other processes in the virus life cycle. The crystallographic studies of 2Apro from enterovirus 71 and its interaction with the substrate are reported here. EV71 2Apro was comprised of an N-terminal domain of four-stranded antiparallel beta-sheet and a C-terminal domain of six-stranded antiparallel beta-barrel with a tightly bound zinc atom. Unlike other 2Apro structures, there is an open cleft across the surface of the protein in an open conformation. As demonstrated by the crystallographic studies and modeling of the complex structure, the open cleft could be fitted with the substrate. On comparison 2Apro of EV71 to those of the human rhinovirus 2 and coxsackievirus B4, the open conformation could be closed with a hinge motion in the bII2 and cII beta-strands. This was supported by molecular dynamic simulation. The structural variation among different 2Apro structures implicates a conformational flexibility in the substrate-binding cleft. The open structure provides an accessible framework for the design and development of therapeutics against the viral target.

Conformational Plasticity of 2A Proteinase from Enterovirus 71.,Cai Q, Yameen M, Liu W, Gao Z, Li Y, Peng X, Cai Y, Wu C, Zheng Q, Li J, Lin T J Virol. 2013 Apr 24. PMID:23616646^[1]

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