5ULW

Structure of human DNA polymerase iota bound to template 1-methyl-deoxyadenosine

5ULW の概要

• エントリーDOI: 10.2210/pdb5ulw/pdb
• 関連するPDBエントリー: 5ULX
• 分子名称: DNA (5'-D(*AP*GP*GP*AP*CP*CP*(DOC))-3'), DNA (5'-D(*TP*(MA7)P*GP*GP*GP*TP*CP*CP*T)-3'), DNA polymerase iota, ... (7 entities in total)
• 機能のキーワード: human dna polymerase iota n1-methyl-deoxyadenosine dttp tls, thansferase-dna complex, thansferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 53015.90

構造登録者

Jain, R.,Aggarwal, A.K. (登録日: 2017-01-25, 公開日: 2017-04-19, 最終更新日: 2023-10-04)

主引用文献

Jain, R.,Choudhury, J.R.,Buku, A.,Johnson, R.E.,Prakash, L.,Prakash, S.,Aggarwal, A.K.
Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-iota.
Sci Rep, 7:43904-43904, 2017

PubMed Abstract: N1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-ι (Polι) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Polι is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Polι bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the syn conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a "foothold" and is largely disordered. Together, our kinetic and structural studies show how Polι maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity.

PubMed: 28272441
DOI: 10.1038/srep43904

実験手法

X-RAY DIFFRACTION (2.617 Å)