title: Functional oligomeric state of avian sarcoma virus integrase.
abstract: Retroviral integrase, one of only three enzymes encoded by the virus, catalyzes the essential step of inserting a DNA copy of the viral genome into the host during infection. Using the avian sarcoma virus integrase, we demonstrate that the enzyme functions as a tetramer. In presteady-state active site titrations, four integrase protomers were required for a single catalytic turnover. Volumetric determination of integrase-DNA complexes imaged by atomic force microscopy during the initial turnover additionally revealed substrate-induced assembly of a tetramer. These results suggest that tetramer formation may be a requisite step during catalysis with ramifications for antiviral design strategies targeting the structurally homologous human immunodeficiency virus, type 1 (HIV-1) integrase.
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Oregon 97331, USA.
authors.forename: Kogan K
authors.initials: KK
authors.lastname: Bao
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Miller
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Erie
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Skalka
authors.forename: Isaac
authors.initials: I
authors.lastname: Wong
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D001358:Avian Sarcoma Viruses / Q000187:drug effects / Q000201:enzymology*; D001665:Binding Sites; D002384:Catalysis; D015195:Drug Design; D019429:Integrase Inhibitors / Q000494:pharmacology; D019426:Integrases / Q000737:chemistry* / Q000502:physiology; D018625:Microscopy, Atomic Force; D008961:Models, Structural
chemical_list: D000998:Antiviral Agents; D019429:Integrase Inhibitors; D019426:Integrases