title: Crystal structures of active and inactive conformations of a caliciviral RNA-dependent RNA polymerase.
abstract: The structure of the RNA-dependent RNA polymerase (RdRP) from the rabbit hemorrhagic disease virus has been determined by x-ray crystallography to a 2.5-A resolution. The overall structure resembles a "right hand," as seen before in other polymerases, including the RdRPs of polio virus and hepatitis C virus. Two copies of the polymerase are present in the asymmetric unit of the crystal, revealing active and inactive conformations within the same crystal form. The fingers and palm domains form a relatively rigid unit, but the thumb domain can adopt either "closed" or "open" conformations differing by a rigid body rotation of approximately 8 degrees. Metal ions bind at different positions in the two conformations and suggest how structural changes may be important to enzymatic function in RdRPs. Comparisons between the structures of the alternate conformational states of rabbit hemorrhagic disease virus RdRP and the structures of RdRPs from hepatitis C virus and polio virus suggest novel structure-function relationships in this medically important class of enzymes.
authors.affiliation: Canadian Institutes for Health Research Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Kenneth K S
authors.initials: KK
authors.lastname: Ng
authors.forename: Maia M
authors.initials: MM
authors.lastname: Cherney
authors.forename: Ana Lopez
authors.initials: AL
authors.lastname: Vazquez
authors.forename: Angeles
authors.initials: A
authors.lastname: Machin
authors.forename: Jose M Martin
authors.initials: JM
authors.lastname: Alonso
authors.forename: Francisco
authors.initials: F
authors.lastname: Parra
authors.forename: Michael N G
authors.initials: MN
authors.lastname: James
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000378:metabolism; D017929:Hemorrhagic Disease Virus, Rabbit / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000378:metabolism; D011817:Rabbits
chemical_list: D012324:RNA-Dependent RNA Polymerase; D054303:HIV Reverse Transcriptase