2O3B

Crystal structure complex of Nuclease A (NucA) with intra-cellular inhibitor NuiA

2O3B の概要

• エントリーDOI: 10.2210/pdb2o3b/pdb
• 関連するPDBエントリー: 1ZM8
• 分子名称: Nuclease, Sugar-non-specific nuclease inhibitor, NICKEL (II) ION, ... (6 entities in total)
• 機能のキーワード: nuclease, nuclease inhibitor, metal complex, non-specific nuclease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Nostoc sp.; 詳細
• 細胞内の位置: Periplasm: P38446
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42041.35

構造登録者

Ghosh, M.,Meiss, G.,Pingoud, A.M.,London, R.E.,Pedersen, L.C. (登録日: 2006-12-01, 公開日: 2006-12-19, 最終更新日: 2023-08-30)

主引用文献

Ghosh, M.,Meiss, G.,Pingoud, A.M.,London, R.E.,Pedersen, L.C.
The nuclease a-inhibitor complex is characterized by a novel metal ion bridge.
J.Biol.Chem., 282:5682-5690, 2007

PubMed Abstract: Nonspecific, extracellular nucleases have received enhanced attention recently as a consequence of the critical role that these enzymes can play in infectivity by overcoming the host neutrophil defense system. The activity of the cyanobacterial nuclease NucA, a member of the betabetaalpha Me superfamily, is controlled by the specific nuclease inhibitor, NuiA. Here we report the 2.3-A resolution crystal structure of the NucA-NuiA complex, showing that NucA inhibition by NuiA involves an unusual divalent metal ion bridge that connects the nuclease with its inhibitor. The C-terminal Thr-135(NuiA) hydroxyl oxygen is directly coordinated with the catalytic Mg(2+) of the nuclease active site, and Glu-24(NuiA) also extends into the active site, mimicking the charge of a scissile phosphate. NuiA residues Asp-75 and Trp-76 form a second interaction site, contributing to the strength and specificity of the interaction. The crystallographically defined interface is shown to be consistent with results of studies using site-directed NuiA mutants. This mode of inhibition differs dramatically from the exosite mechanism of inhibition seen with the DNase colicins E7/E9 and from other nuclease-inhibitor complexes that have been studied. The structure of this complex provides valuable insights for the development of inhibitors for related nonspecific nucleases that share the DRGH active site motif such as the Streptococcus pneumoniae nuclease EndA, which mediates infectivity of this pathogen, and mitochondrial EndoG, which is involved in recombination and apoptosis.

PubMed: 17138564
DOI: 10.1074/jbc.M605986200

実験手法

X-RAY DIFFRACTION (2.3 Å)