7AYY

Structure of the human 8-oxoguanine DNA Glycosylase hOGG1 in complex with activator TH10785

これはPDB形式変換不可エントリーです。

7AYY の概要

• エントリーDOI: 10.2210/pdb7ayy/pdb
• 分子名称: N-glycosylase/DNA lyase, ~{N}-cyclohexyl-2-cyclopropyl-quinazolin-4-amine, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: 8-oxoguanine dna glycosylase, n-glycosylase, dna lyase, dna repair, dna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 191716.14

構造登録者

Masuyer, G.,Davies, J.R.,Stenmark, P. (登録日: 2020-11-13, 公開日: 2022-06-01, 最終更新日: 2024-01-31)

主引用文献

Michel, M.,Benitez-Buelga, C.,Calvo, P.A.,Hanna, B.M.F.,Mortusewicz, O.,Masuyer, G.,Davies, J.,Wallner, O.,Sanjiv, K.,Albers, J.J.,Castaneda-Zegarra, S.,Jemth, A.S.,Visnes, T.,Sastre-Perona, A.,Danda, A.N.,Homan, E.J.,Marimuthu, K.,Zhenjun, Z.,Chi, C.N.,Sarno, A.,Wiita, E.,von Nicolai, C.,Komor, A.J.,Rajagopal, V.,Muller, S.,Hank, E.C.,Varga, M.,Scaletti, E.R.,Pandey, M.,Karsten, S.,Haslene-Hox, H.,Loevenich, S.,Marttila, P.,Rasti, A.,Mamonov, K.,Ortis, F.,Schomberg, F.,Loseva, O.,Stewart, J.,D'Arcy-Evans, N.,Koolmeister, T.,Henriksson, M.,Michel, D.,de Ory, A.,Acero, L.,Calvete, O.,Scobie, M.,Hertweck, C.,Vilotijevic, I.,Kalderen, C.,Osorio, A.,Perona, R.,Stolz, A.,Stenmark, P.,Berglund, U.W.,de Vega, M.,Helleday, T.
Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function.
Science, 376:1471-1476, 2022

PubMed Abstract: Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed β,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.

PubMed: 35737787
DOI: 10.1126/science.abf8980

実験手法

X-RAY DIFFRACTION (2 Å)