3uq2 | pdb_00003uq2

Crystal structure of the post-catalytic product complex of polymerase lambda with an rCMP inserted opposite a templating G and dAMP inserted opposite a templating T at the primer terminus.

spinqualitylabelsall models 3uq2, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3uq2 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, NA, PPV Related: 3mgh, 3mgi, 3upq, 3uq0, 3uq1 Gene: POLL (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DPOLL_HUMAN] Repair polymerase. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Has both DNA polymerase and terminal transferase activities. Has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity. Publication Abstract from PubMed Although most DNA polymerases discriminate against ribonucleotide triphosphaets (rNTPs) during DNA synthesis, recent studies have shown that large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome. Here, we investigate how a DNA polymerase can stably incorporate an rNTP. The X-ray crystal structure of a variant of human DNA polymerase lambda reveals that the rNTP occupies the nucleotide binding pocket without distortion of the active site, despite an unfavorable interaction between the 2'-O and Tyr505 backbone carbonyl. This indicates an energetically unstable binding state for the rNTP, stabilized by additional protein-nucleotide interactions. Supporting this idea is the 200-fold lower catalytic efficiency for rNTP relative to deoxyribonucleotide triphosphate (dNTP) incorporation, reflecting a higher apparent Km value for the rNTP. Furthermore, distortion observed in the structure of the post-catalytic product complex suggests that once the bond between the alpha- and beta-phosphates of the rNTP is broken, the unfavorable binding state of the ribonucleotide cannot be maintained. Finally, structural and biochemical evaluation of dNTP insertion onto an ribonucleotide monophosphate (rNMP)-terminated primer indicates that a primer-terminal rNMP does not impede extension. The results are relevant to how ribonucleotides are incorporated into DNA in vivo, during replication and during repair, perhaps especially in non-proliferating cells when rNTP:dNTP ratios are high. The catalytic cycle for ribonucleotide incorporation by human DNA Pol lambda,Gosavi RA, Moon AF, Kunkel TA, Pedersen LC, Bebenek K Nucleic Acids Res. 2012 May 14. PMID:22584622 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase

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