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Structures of the Leishmania infantum polymerase beta
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2014
- Publisher :
- Elsevier, 2014.
-
Abstract
- 9 p.-4 fig.-4 tab.<br />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.<br />This work was supported by R01-GM100021 and R00 ES015421 to MGD. AA and VL thank the Fundacion Ramon Areces and MICINN (AGL2010-21806-C02-01) for funding.
- Subjects :
- Models, Molecular
Protein Folding
DNA polymerase
Protein Conformation
DNA polymerase II
DNA repair
Crystallography, X-Ray
Biochemistry
DNA polymerase delta
Protein Structure, Secondary
Article
Catalytic Domain
Leishmania infantum
Protein Structure, Quaternary
Molecular Biology
Leishmaniasis
Polymerase
DNA Polymerase beta
Genetics
DNA clamp
biology
Sequence Homology, Amino Acid
DNA replication
Cell Biology
Processivity
Molecular biology
Mutation
biology.protein
DNA polymerase mu
Family X
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....703671977cd002edb052cddcb046c36d