2w1v | pdb_00002w1v
CRYSTAL STRUCTURE OF MOUSE NITRILASE-2 AT 1.4A RESOLUTION
Structural highlights
Function[NIT2_MOUSE] Has a omega-amidase activity. The role of omega-amidase is to remove potentially toxic intermediates by converting alpha-ketoglutaramate and alpha-ketosuccinamate to biologically useful alpha-ketoglutarate and oxaloacetate, respectively.[1] Publication Abstract from PubMedNitrilases 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. Functional Proteomic and Structural Insights into Molecular Recognition in the Nitrilase Family Enzymes (dagger) (double dagger).,Barglow KT, Saikatendu KS, Bracey MH, Huey R, Morris GM, Olson AJ, Stevens RC, Cravatt BF Biochemistry. 2008 Nov 24. PMID:19053248[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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