2W1V

Crystal structure of mouse nitrilase-2 at 1.4A resolution

2W1V の概要

• エントリーDOI: 10.2210/pdb2w1v/pdb
• 分子名称: NITRILASE HOMOLOG 2 (2 entities in total)
• 機能のキーワード: hydrolase, nitrilase
• 由来する生物種: MUS MUSCULUS (MOUSE)
• 細胞内の位置: Cytoplasm (By similarity): Q9JHW2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61071.41

構造登録者

Barglow, K.T.,Saikatendu, K.S.,Stevens, R.C.,Cravatt, B.F. (登録日: 2008-10-21, 公開日: 2008-12-16, 最終更新日: 2023-12-13)

主引用文献

Barglow, K.T.,Saikatendu, K.S.,Bracey, M.H.,Huey, R.,Morris, G.M.,Olson, A.J.,Stevens, R.C.,Cravatt, B.F.
Functional Proteomic and Structural Insights Into Molecular Recognition in the Nitrilase Family Enzymes.
Biochemistry, 47:13514-, 2008

PubMed Abstract: Nitrilases are a large and diverse family of nonpeptidic C-N hydrolases. The mammalian genome encodes eight nitrilase enzymes, several of which remain poorly characterized. Prominent among these are nitrilase-1 (Nit1) and nitrilase-2 (Nit2), which, despite having been shown to exert effects on cell growth and possibly serving as tumor suppressor genes, are without known substrates or selective inhibitors. In previous studies, we identified several nitrilases, including Nit1 and Nit2, as targets for dipeptide-chloroacetamide activity-based proteomics probes. Here, we have used these probes, in combination with high-resolution crystallography and molecular modeling, to systematically map the active site of Nit2 and identify residues involved in molecular recognition. We report the 1.4 A crystal structure of mouse Nit2 and use this structure to identify residues that discriminate probe labeling between the Nit1 and Nit2 enzymes. Interestingly, some of these residues are conserved across all vertebrate Nit2 enzymes and, conversely, not found in any vertebrate Nit1 enzymes, suggesting that they are key discriminators of molecular recognition between these otherwise highly homologous enzymes. Our findings thus point to a limited set of active site residues that establish distinct patterns of molecular recognition among nitrilases and provide chemical probes to selectively perturb the function of these enzymes in biological systems.

PubMed: 19053248
DOI: 10.1021/BI801786Y

実験手法

X-RAY DIFFRACTION (1.49 Å)