6w13

From Proteopedia

Human 8-oxoguanine glycosylase interrogating fully intrahelical oxoG lesion DNA

Structural highlights

6w13 is a 3 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 2.38Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

OGG1_HUMAN Defects in OGG1 may be a cause of renal cell carcinoma (RCC) [MIM:144700. It is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.

Function

OGG1_HUMAN DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion.

Publication Abstract from PubMed

Efficient search for DNA damage embedded in vast expanses of the DNA genome presents one of the greatest challenges to DNA repair enzymes. We report here crystal structures of human 8-oxoguanine (oxoG) DNA glycosylase, hOGG1, that interact with the DNA containing the damaged base oxoG and the normal base G while they are nested in the DNA helical stack. The structures reveal that hOGG1 engages the DNA using different protein-DNA contacts from those observed in the previously determined lesion recognition complex and other hOGG1-DNA complexes. By applying molecular dynamics simulations, we have determined the pathways taken by the lesion and normal bases when extruded from the DNA helix and their associated free energy profiles. These results reveal how the human oxoG DNA glycosylase hOGG1 locates the lesions inside the DNA helix and facilitates their extrusion for repair.

The trajectory of intrahelical lesion recognition and extrusion by the human 8-oxoguanine DNA glycosylase.,Shigdel UK, Ovchinnikov V, Lee SJ, Shih JA, Karplus M, Nam K, Verdine GL Nat Commun. 2020 Sep 7;11(1):4437. doi: 10.1038/s41467-020-18290-2. PMID:32895378^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shigdel UK, Ovchinnikov V, Lee SJ, Shih JA, Karplus M, Nam K, Verdine GL. The trajectory of intrahelical lesion recognition and extrusion by the human 8-oxoguanine DNA glycosylase. Nat Commun. 2020 Sep 7;11(1):4437. PMID:32895378 doi:10.1038/s41467-020-18290-2