6nku

Ternary complex crystal structure of DNA polymerase Beta with "hot-spot sequence" with dGTP

spinqualitylabelsall models 6nku, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nku is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: 2DT, CL, DGT, MG, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DPOLB_HUMAN Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases. Publication Abstract from PubMed The human DNA polymerase (pol) beta cancer variant K289M has altered polymerase activity in vitro, and the structure of wild-type pol beta reveals that the K289 side chain contributes to a network of stabilizing interactions in a C-terminal region of the enzyme distal to the active site. Here, we probed the capacity of the K289M variant to tolerate strain introduced within the C-terminal region and active site. Strain was imposed by making use of a dGTP analogue containing a CF2 group substitution for the beta-gamma bridging oxygen atom. The ternary complex structure of the K289M variant displays an alteration in the C-terminal region, whereas the structure of wild-type pol beta is not altered in the presence of the dGTP CF2 analogue. The alteration in the K289M variant impacts the active site, because the enzyme in the ternary complex fails to adopt the normal open to closed conformational change and assembly of the catalytically competent active site. These results reveal the importance of the K289-mediated stabilizing network in the C-terminal region of pol beta and suggest an explanation for why the K289M cancer variant is deficient in polymerase activity even though the position 289 side chain is distal to the active site. Revealing an Internal Stabilization Deficiency in the DNA Polymerase beta K289M Cancer Variant through the Combined Use of Chemical Biology and X-ray Crystallography.,Batra VK, Alnajjar KS, Sweasy JB, McKenna CE, Goodman MF, Wilson SH Biochemistry. 2020 Mar 3;59(8):955-963. doi: 10.1021/acs.biochem.9b01072. Epub, 2020 Feb 12. PMID:31999437 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase 3D structures

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