2O3H

Crystal structure of the human C65A Ape

2O3H の概要

• エントリーDOI: 10.2210/pdb2o3h/pdb
• 関連するPDBエントリー: 2o3C
• 分子名称: DNA-(apurinic or apyrimidinic site) lyase, SAMARIUM (III) ION, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: ape, endonuclease, lyase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus. DNA-(apurinic or apyrimidinic site) lyase, mitochondrial: Mitochondrion: P27695
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32548.27

構造登録者

Georgiadis, M.M.,Gaur, R.K.,Delaplane, S.,Svenson, J. (登録日: 2006-12-01, 公開日: 2007-12-11, 最終更新日: 2023-08-30)

主引用文献

Georgiadis, M.M.,Luo, M.,Gaur, R.K.,Delaplane, S.,Li, X.,Kelley, M.R.
Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease
Mutat.Res., 643:54-63, 2008

PubMed Abstract: Human apurinic/apyrimidinic endonuclease (hApe1) encodes two important functional activities: an essential base excision repair (BER) activity and a redox activity that regulates expression of a number of genes through reduction of their transcription factors, AP-1, NFkappaB, HIF-1alpha, CREB, p53 and others. The BER function is highly conserved from prokaryotes (E. coli exonuclease III) to humans (hApe1). Here, we provide evidence supporting a redox function unique to mammalian Apes. An evolutionary analysis of Ape sequences reveals that, of the 7 Cys residues, Cys 93, 99, 208, 296, and 310 are conserved in both mammalian and non-mammalian vertebrate Apes, while Cys 65 is unique to mammalian Apes. In the zebrafish Ape (zApe), selected as the vertebrate sequence most distant from human, the residue equivalent to Cys 65 is Thr 58. The wild-type zApe enzyme was tested for redox activity in both in vitro EMSA and transactivation assays and found to be inactive, similar to C65A hApe1. Substitution of Thr 58 with Cys in zApe, however, resulted in a redox active enzyme, suggesting that a Cys residue in this position is indeed critical for redox function. In order to further probe differences between redox active and inactive enzymes, we have determined the crystal structures of vertebrate redox inactive enzymes, the C65A human Ape1 enzyme and the zApe enzyme at 1.9 and 2.3A, respectively. Our results provide new insights on the redox function and highlight a dramatic gain-of-function activity for Ape1 in mammals not found in non-mammalian vertebrates or lower organisms.

PubMed: 18579163
DOI: 10.1016/j.mrfmmm.2008.04.008

実験手法

X-RAY DIFFRACTION (1.9 Å)