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Publication Abstract from PubMed

The adenovirus proteinase (AVP), the first member of a new class of cysteine proteinases, is essential for the production of infectious virus, and here we report its structure at 0.98 A-resolution. AVP, initially synthesized as an inactive enzyme, requires two cofactors for maximal activity- pVIc, an 11 amino acid peptide, and the viral DNA. Comparison of the structure of AVP with that of an active form the AVP-pVIc complex reveals why AVP is inactive. Both forms have an alpha + beta fold; the major structural differences between them lie in the beta-sheet domain. In AVP-pVIc, the general base His54 Ndelta is 3.9 A from the Cys122 Sgamma thereby rendering it nucleophilic. In AVP, however, His54 Ndelta is 7.0 A away Cys122 Sgamma, too far away to be able to abstract the proton from Cys122. In AVP-pVIc, Tyr84 forms a cation-pi interaction with His54 that should raise the pKa of His54 and freeze the imidazole ring in the place optimal for forming an ion pair with Cys122. In AVP, however, Tyr84 is more than 11 A away from its position in AVP-pVIc. Based on the structural differences between AVP and AVP-pVIc, we present a model which postulates activation of AVP by pVIc occurs via a 62-amino acid long activation pathway in which the binding of pVIc initiates contiguous conformational changes, like falling dominos: There is a common pathway that branches into a pathway that leads to the repositioning of His54 and another pathway that leads to the repositioning of Tyr84.

Regulation of a viral proteinase by a peptide and DNA in one-dimensional space. III. atomic resolution structure of the nascent form of the adenovirus proteinase.,Baniecki ML, McGrath WJ, Mangel WF J Biol Chem. 2012 Oct 7. PMID:23043139^[1]

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