1vsm
ASV INTEGRASE CORE DOMAIN IN CITRATE BUFFER PH 5.0
Structural highlights
FunctionPOL_RSVSB Capsid protein p27: Self-associates to form the irregular polyhedron core composed of hexamers and pentamers, that encapsulates the genomic RNA-nucleocapsid complex. Assembles as a tube in vitro. Binds to inositol hexakisphosphate (IP6), which allows the assembly of the polyhedral capsid.[UniProtKB:P03322] Plays a role in the oligomerization of the Gag polyprotein and in the stabilization of the immature particle. Essential layering element during tube assembly. Allows the cooperative binging of Gag to the host plasma membrane.[UniProtKB:P03322] Binds strongly to viral nucleic acids and promotes their packaging (By similarity). Plays a role in the maturation-stabilization of the viral dimeric RNA via highly structured zinc-binding motifs (By similarity).[UniProtKB:P03322][UniProtKB:P0C776] The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell.[PROSITE-ProRule:PRU00275] Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions (PubMed:9218451). This recombination event is an essential step in the viral replication cycle. Has a strong preference for using the 3'-OH at the viral DNA end as a nucleophile.[UniProtKB:P03354][1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCrystallographic studies of the catalytic core domain of avian sarcoma virus integrase (ASV IN) have provided the most detailed picture so far of the active site of this enzyme, which belongs to an important class of targets for designing drugs against AIDS. Recently, crystals of an inactive D64N mutant were obtained under conditions identical to those used for the native enzyme. Data were collected at different pH values and in the presence of divalent cations. Data were also collected at low pH for the crystals of the native ASV IN core domain. In the structures of native ASV IN at pH 6.0 and below, as well as in all structures of the D64N mutants, the side chain of the active site residue Asx-64 (Asx denotes Asn or Asp) is rotated by approximately 150 degrees around the Calpha---Cbeta bond, compared with the structures at higher pH. In the new structures, this residue makes hydrogen bonds with the amide group of Asn-160, and thus, the usual metal-binding site, consisting of Asp-64, Asp-121, and Glu-157, is disrupted. Surprisingly, however, a single Zn2+ can still bind to Asp-121 in the mutant, without restoration of the activity of the enzyme. These structures have elucidated an unexpected mechanism of inactivation of the enzyme by lowering the pH or by mutation, in which a protonated side chain of Asx-64 changes its orientation and interaction partner. Structural basis for inactivating mutations and pH-dependent activity of avian sarcoma virus integrase.,Lubkowski J, Yang F, Alexandratos J, Merkel G, Katz RA, Gravuer K, Skalka AM, Wlodawer A J Biol Chem. 1998 Dec 4;273(49):32685-9. PMID:9830010[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
