2W1V

Crystal structure of mouse nitrilase-2 at 1.4A resolution

Summary for 2W1V

• Entry DOI: 10.2210/pdb2w1v/pdb
• Descriptor: NITRILASE HOMOLOG 2 (2 entities in total)
• Functional Keywords: hydrolase, nitrilase
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Cytoplasm (By similarity): Q9JHW2
• Total number of polymer chains: 2
• Total formula weight: 61071.41

Authors

Barglow, K.T.,Saikatendu, K.S.,Stevens, R.C.,Cravatt, B.F. (deposition date: 2008-10-21, release date: 2008-12-16, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.49 Å)