PDBsum entry 4fvb

Hydrolase

PDB id: 4fvb

Contents

Protein chain

138 a.a.

Metals

_ZN

Waters ×115

PDB id:

4fvb

Name:

Hydrolase

Title:

Crystal structure of ev71 2a proteinase c110a mutant

Structure:

2a proteinase. Chain: a. Engineered: yes. Mutation: yes

Source:

Human enterovirus 71. Organism_taxid: 39054. Strain: e2004104-tw-cdc. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.197 R-free: 0.240

Authors:

Q.Cai,Y.Muhammad,W.Liu,Z.Gao,X.Peng,Y.Cai,C.Wu,Q.Zheng,J.Li,T.Lin

Key ref:

Q.Cai et al. (2013). Conformational plasticity of the 2A proteinase from enterovirus 71. J Virol, 87, 7348-7356. PubMed id: 23616646 DOI: 10.1128/JVI.03541-12

Date:

29-Jun-12 Release date: 19-Jun-13

Protein chain

A9XG43  (A9XG43_HE71) -  Genome polyprotein from Human enterovirus 71

Seq: 2193 a.a.

Struc: 138 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 3: E.C.3.4.22.28 - picornain 3C.
• Reaction: Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
• Enzyme class 4: E.C.3.4.22.29 - picornain 2A.
• Reaction: Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
• Enzyme class 5: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1128/JVI.03541-12

J Virol 87:7348-7356 (2013)

PubMed id: 23616646

Conformational plasticity of the 2A proteinase from enterovirus 71.

Q.Cai, M.Yameen, W.Liu, Z.Gao, Y.Li, X.Peng, Y.Cai, C.Wu, Q.Zheng, J.Li, T.Lin.

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.