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7EF8

Crystal structure of mouse MUTYH in complex with DNA containing AP site analogue:8-oxoG (Form I)

Summary for 7EF8
Entry DOI10.2210/pdb7ef8/pdb
DescriptorAdenine DNA glycosylase, DNA (5'-D(*TP*GP*AP*GP*AP*CP*(8OG)P*GP*GP*GP*AP*CP*T)-3'), DNA (5'-D(*TP*AP*GP*TP*CP*CP*CP*(3DR)P*GP*TP*CP*TP*C)-3'), ... (7 entities in total)
Functional Keywordsdna repair, dna binding protein-dna complex, dna binding protein/dna
Biological sourceMus musculus (Mouse)
More
Total number of polymer chains3
Total formula weight60768.12
Authors
Nakamura, T.,Nakabeppu, Y.,Yamagata, Y. (deposition date: 2021-03-21, release date: 2021-06-23, Last modification date: 2023-11-29)
Primary citationNakamura, T.,Okabe, K.,Hirayama, S.,Chirifu, M.,Ikemizu, S.,Morioka, H.,Nakabeppu, Y.,Yamagata, Y.
Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer.
Nucleic Acids Res., 49:7154-7163, 2021
Cited by
PubMed Abstract: Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9-Rad1-Hus1 complex (9-1-1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function.
PubMed: 34142156
DOI: 10.1093/nar/gkab492
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.45 Å)
Structure validation

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