4EKF
Structure of the Inactive Adenovirus Proteinase at 0.98 Angstrom Resolution
Summary for 4EKF
Entry DOI | 10.2210/pdb4ekf/pdb |
Related | 1NLN |
Descriptor | Adenain, SODIUM ION (3 entities in total) |
Functional Keywords | alpha and beta protein (a+b), hydrolase |
Biological source | Human adenovirus 2 |
Cellular location | Virion : P03252 |
Total number of polymer chains | 1 |
Total formula weight | 23169.34 |
Authors | Baniecki, M.L.,McGrath, W.J.,Mangel, W.F. (deposition date: 2012-04-09, release date: 2012-10-10, Last modification date: 2024-11-20) |
Primary citation | Baniecki, M.L.,McGrath, W.J.,Mangel, W.F. 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. J.Biol.Chem., 288:2081-2091, 2013 Cited by PubMed Abstract: 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 Å 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 α + β fold; the major structural differences between them lie in the β-sheet domain. In AVP-pVIc, the general base His-54 Nδ1 is 3.9 Å away from the Cys-122 Sγ, thereby rendering it nucleophilic. In AVP, however, His-54 Nδ1 is 7.0 Å away from Cys-122 Sγ, too far away to be able to abstract the proton from Cys-122. In AVP-pVIc, Tyr-84 forms a cation-π interaction with His-54 that should raise the pK(a) of His-54 and freeze the imidazole ring in the place optimal for forming an ion pair with Cys-122. In AVP, however, Tyr-84 is more than 11 Å away from its position in AVP-pVIc. Based on the structural differences between AVP and AVP-pVIc, we present a model that postulates that activation of AVP by pVIc occurs via a 62-amino acid-long activation pathway in which the binding of pVIc initiates contiguous conformational changes, analogous to falling dominos. There is a common pathway that branches into a pathway that leads to the repositioning of His-54 and another pathway that leads to the repositioning of Tyr-84. PubMed: 23043139DOI: 10.1074/jbc.M112.407429 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (0.98 Å) |
Structure validation
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