title: Structures of the Leishmania infantum polymerase beta.
abstract: Protozoans of the genus Leishmania, the pathogenic agent causing leishmaniasis, encode the family X DNA polymerase Li Pol β. Here, we report the first crystal structures of Li Pol β. Our pre- and post-catalytic structures show that the polymerase adopts the common family X DNA polymerase fold. However, in contrast to other family X DNA polymerases, the dNTP-induced conformational changes in Li Pol β are much more subtle. Moreover, pre- and post-catalytic structures reveal that Li Pol β interacts with the template strand through a nonconserved, variable region known as loop3. Li Pol β Δloop3 mutants display a higher catalytic rate, catalytic efficiency and overall error rates with respect to WT Li Pol β. These results further demonstrate the subtle structural variability that exists within this family of enzymes and provides insight into how this variability underlies the substantial functional differences among their members.
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, BST 7-169, Stony Brook, NY 11794-8651, USA.
authors.forename: Edison
authors.initials: E
authors.lastname: Mejia
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, BST 7-169, Stony Brook, NY 11794-8651, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Burak
authors.affiliation: Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Larraga
authors.affiliation: Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
authors.affiliation: Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. Electronic address: bebenek@niehs.nih.gov.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bebenek
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, BST 7-169, Stony Brook, NY 11794-8651, USA. Electronic address: miguel.garcia-diaz@stonybrook.edu.
authors.forename: Miguel
authors.initials: M
authors.lastname: Garcia-Diaz
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D018314:Leishmania infantum / Q000201:enzymology*; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D019951:DNA Polymerase beta
keywords: DNA polymerase; DNA repair; Family X; Leishmaniasis