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Catalytic Site Atlas

CSA LITERATURE entry for 1nln

E.C. nameadenain
SpeciesHuman adenovirus 2 (Virus)
E.C. Number (IntEnz) 3.4.22.39
CSA Homologues of 1nln1avp,
CSA Entries With UniProtID P03252
CSA Entries With EC Number 3.4.22.39
PDBe Entry 1nln
PDBSum Entry 1nln
MACiE Entry 1nln

Literature Report

IntroductionHuman adenovirus proteinase is a cysteine proteinase required for the synthesis of infectious virus. Cofactors discovered include viral DNA, or a short oligopeptide which the enzyme itself cleaves out. The enzyme cleaves specific Gly-Ala peptides in a number of viral precursor proteins, and also cleaves host cell cytoskeleton keratins.
The structure and mechanism of this enzyme suggest convergent evolution to give a catalytic mechanism similar to papain.
MechansimThis enzyme has a virtually identical mechanism to the cysteine proteinase papain. The pKa of the thiol residue of Cys 122 is lowered by the action of His 54 as a general base catalyst which abstracts the cysteine proton. This allows the thiolate ion to acts as a nucleophile in attack of the carbonyl carbon. The tetrahedral transition state is stabilised by the oxyanion hole formed by Gln 115. Glu 71 activates His 54, which is able to act as a general acid catalyst in protonating the leaving group to facilitate cleavage of the scissile bond. His 54 then activates water by proton abstraction to cleave the acyl-enzyme intermediate.
Reaction

Catalytic Sites for 1nln

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA5454macie:sideChainActs as a general acid/base catalyst to activate the Cys 122 and water for nucleophilic attack, and to facilitate collapse of the intermediate towards cleavage of the scissile bond.
CysA122122macie:sideChainActs as a nucleophile to attack the carbonyl carbon of the substrate.
GluA7171macie:sideChainActivates His 54.
GlnA115115macie:sideChainForms the oxyanion hole to stabilise the transition state.

Literature References

Notes:
McGrath WJ
Crystallographic structure at 1.6-A resolution of the human adenovirus proteinase in a covalent complex with its 11-amino-acid peptide cofactor: insights on a new fold.
Biochim Biophys Acta 2003 1648 1-11
PubMed: 12758141
Ding J
Crystal structure of the human adenovirus proteinase with its 11 amino acid cofactor.
EMBO J 1996 15 1778-1783
PubMed: 8617222
Grierson AW
The protease of adenovirus serotype 2 requires cysteine residues for both activation and catalysis.
J Gen Virol 1994 75 ( Pt 10) 2761-2764
PubMed: 7931163
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