4FVD

Crystal structure of EV71 2A proteinase C110A mutant in complex with substrate

Summary for 4FVD

• Entry DOI: 10.2210/pdb4fvd/pdb
• Related: 4FVB 4FVE 4FVH 4FVI
• Descriptor: 2A proteinase, 10-mer peptide from 2A proteinase, ZINC ION, ... (4 entities in total)
• Functional Keywords: hydrolase, cysteine proteinase, hydrolase-hydrolase substrate complex, hydrolase/hydrolase substrate
• Biological source: Human enterovirus 71; More
• Cellular location: Picornain 3C: Host cytoplasm (By similarity). Protein 3B: Virion (By similarity): A9XG43 A9XG43
• Total number of polymer chains: 2
• Total formula weight: 17753.08

Authors

Cai, Q.,Muhammad, Y.,Liu, W.,Gao, Z.,Peng, X.,Cai, Y.,Wu, C.,Zheng, Q.,Li, J.,Lin, T. (deposition date: 2012-06-29, release date: 2013-06-19, Last modification date: 2023-11-08)

Primary citation

Cai, Q.,Yameen, M.,Liu, W.,Gao, Z.,Li, Y.,Peng, X.,Cai, Y.,Wu, C.,Zheng, Q.,Li, J.,Lin, T.
Conformational Plasticity of 2A Proteinase from Enterovirus 71
J.Virol., 87:7348-7356, 2013

PubMed Abstract: The 2A proteinase (2A(pro)) is an enterovirally encoded cysteine protease that plays essential roles in both the processing of viral precursor polyprotein and the hijacking of host cell translation and other processes in the virus life cycle. Crystallographic studies of 2A(pro) from enterovirus 71 (EV71) and its interaction with the substrate are reported here. EV71 2A(pro) was comprised of an N-terminal domain of a four-stranded antiparallel β sheet and a C-terminal domain of a six-stranded antiparallel β barrel with a tightly bound zinc atom. Unlike in other 2A(pro) 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 2A(pro) 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 β strands. This was supported by molecular dynamic simulation. The structural variation among different 2A(pro) structures indicates 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.

PubMed: 23616646
DOI: 10.1128/JVI.03541-12

Experimental method

X-RAY DIFFRACTION (1.66 Å)