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http://purl.uniprot.org/citations/17475573http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17475573http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17475573http://www.w3.org/2000/01/rdf-schema#comment"The incorporation of dNMPs into DNA by polymerases involves a phosphoryl transfer reaction hypothesized to require two divalent metal ions. Here we investigate this hypothesis using as a model human DNA polymerase lambda (Pol lambda), an enzyme suggested to be activated in vivo by manganese. We report the crystal structures of four complexes of human Pol lambda. In a 1.9 A structure of Pol lambda containing a 3'-OH and the non-hydrolyzable analog dUpnpp, a non-catalytic Na+ ion occupies the site for metal A and the ribose of the primer-terminal nucleotide is found in a conformation that positions the acceptor 3'-OH out of line with the alpha-phosphate and the bridging oxygen of the pyrophosphate leaving group. Soaking this crystal in MnCl2 yielded a 2.0 A structure with Mn2+ occupying the site for metal A. In the presence of Mn2+, the conformation of the ribose is C3'-endo and the 3'-oxygen is in line with the leaving oxygen, at a distance from the phosphorus atom of the alpha-phosphate (3.69 A) consistent with and supporting a catalytic mechanism involving two divalent metal ions. Finally, soaking with MnCl2 converted a pre-catalytic Pol lambda/Na+ complex with unreacted dCTP in the active site into a product complex via catalysis in the crystal. These data provide pre- and post-transition state information and outline in a single crystal the pathway for the phosphoryl transfer reaction carried out by DNA polymerases."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.org/dc/terms/identifier"doi:10.1016/j.dnarep.2007.03.005"xsd:string
http://purl.uniprot.org/citations/17475573http://purl.org/dc/terms/identifier"doi:10.1016/j.dnarep.2007.03.005"xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Bebenek K."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Bebenek K."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Kunkel T.A."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Kunkel T.A."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Garcia-Diaz M."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Garcia-Diaz M."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Pedersen L.C."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Pedersen L.C."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Krahn J.M."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/author"Krahn J.M."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/name"DNA Repair"xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/name"DNA Repair"xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/pages"1333-1340"xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/pages"1333-1340"xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/title"Role of the catalytic metal during polymerization by DNA polymerase lambda."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/title"Role of the catalytic metal during polymerization by DNA polymerase lambda."xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/volume"6"xsd:string
http://purl.uniprot.org/citations/17475573http://purl.uniprot.org/core/volume"6"xsd:string