6vkp | pdb_00006vkp

Crystal structure of DPO4 extension past 8-oxoadenine (oxoA) and dG

spinqualitylabelsall models 6vkp, resolution 2.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vkp is a 6 chain structure with sequence from Homo sapiens and Saccharolobus solfataricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.54Å Ligands: A38, DZ4, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DPO4_SACS2 Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis. Publication Abstract from PubMed Nucleobases within DNA are attacked by reactive oxygen species to produce 7,8-dihydro-8-oxoguanine (oxoG) and 7,8-dihydro-8-oxoadenine (oxoA) as major oxidative lesions. The high mutagenicity of oxoG is attributed to the lesion's ability to adopt syn-oxoG:anti-dA with Watson-Crick-like geometry. Recent studies have revealed that Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) inserts nucleotide opposite oxoA in an error-prone manner and accommodates syn-oxoA:anti-dGTP with Watson-Crick-like geometry, highlighting a promutagenic nature of oxoA. To gain further insights into the bypass of oxoA by Dpo4, we have conducted kinetic and structural studies of Dpo4 extending oxoA:dT and oxoA:dG by incorporating dATP opposite templating dT. The extension past oxoA:dG was approximately 5-fold less efficient than that past oxoA:dT. Structural studies revealed that Dpo4 accommodated dT:dATP base pair past anti-oxoA:dT with little structural distortion. In the Dpo4-oxoA:dG extension structure, oxoA was in an anti conformation and did not form hydrogen bonds with the primer terminus base. Unexpectedely, the dG opposite oxoA exited the primer terminus site and resided in an extrahelical site, where it engaged in minor groove contacts to the two immediate upstream bases. The extrahelical dG conformation appears to be induced by the stabilization of anti-oxoA conformation via bifurcated hydrogen bonds with Arg332. This unprecedented structure suggests that Dpo4 may use Arg332 to sense 8-oxopurines at the primer terminus site and slow the extension from the mismatch by promoting anti conformation of 8-oxopurines. Insights into the mismatch discrimination mechanism of Y-family DNA polymerase Dpo4.,Jung H, Lee S Biochem J. 2021 May 14;478(9):1769-1781. doi: 10.1042/BCJ20210162. PMID:33881499 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA