The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis.
The crystal structure of the 2A proteinase from human rhinovirus serotype 2 (HRV2-2A(pro)) has been solved to 1.95 A resolution. The structure has an unusual, although chymotrypsin-related, fold comprising a unique four-stranded beta sheet as the N-terminal domain and a six-stranded beta barrel as the C-terminal domain. A tightly bound zinc ion, essential for the stability of HRV2-2A(pro), is tetrahedrally coordinated by three cysteine sulfurs and one histidine nitrogen. The active site consists of a catalytic triad formed by His18, Asp35 and Cys106. Asp35 is additionally involved in an extensive hydrogen-bonding network. Modelling studies reveal a substrate-induced fit that explains the specificity of the subsites S4, S2, S1 and S1'. The structure of HRV2-2A(pro) suggests the mechanism of the cis cleavage and its release from the polyprotein.
Petersen
J F
JF
MRC Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.
Cherney
M M
MM
Liebig
H D
HD
Skern
T
T
Kuechler
E
E
James
M N
MN
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D002918:Chymotrypsin / Q000737:chemistry; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012229:Rhinovirus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014764:Viral Proteins; D015032:Zinc / Q000378:metabolism
D011994:Recombinant Proteins; D014764:Viral Proteins; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus; D015032:Zinc