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Publication Abstract from PubMed

Glycosylasparaginase belongs to a family of N-terminal nucleophile hydrolases that autoproteolytically generate their mature enzymes from single-chain protein precursors. Previously, based on a precursor structure paused at pre-autoproteolysis stage by a reversible inhibitor (glycine), we proposed a mechanism of intramolecular autoproteolysis. A key structural feature, a highly strained conformation at the scissile peptide bond, had been identified and was hypothesized to be critical for driving autoproteolysis through an N-O acyl shift. To examine this "twist-and-break" hypothesis, we report here a 1. 9-A-resolution structure of an autoproteolysis-active precursor (a T152C mutant) that is free of inhibitor or ligand and is poised to undergo autoproteolysis. The current crystallographic study has provided direct evidence for the natural conformation of the glycosylasparaginase autocatalytic site without influence from any inhibitor or ligand. This finding has confirmed our previous proposal that conformational strain is an intrinsic feature of an active precursor.

Crystallographic snapshot of glycosylasparaginase precursor poised for autoprocessing.,Wang Y, Guo HC J Mol Biol. 2010 Oct 15;403(1):120-30. Epub 2010 Aug 26. PMID:20800597^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.