2gaw: Difference between revisions
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==Overview== | ==Overview== | ||
Glycosylasparaginase (GA) is a member of a novel family of N-terminal, nucleophile hydrolases that catalytically use an N-terminal residue as, both a polarizing base and a nucleophile. These enzymes are activated from, a single chain precursor by intramolecular autoproteolysis to yield the, N-terminal nucleophile. A deficiency of GA results in the human genetic, disorder known as aspartylglycosaminuria. In this study, we report the, crystal structure of recombinant GA from Flavobacterium meningosepticum., Similar to the human structure, the bacterial GA forms an, alphabetabetaalpha sandwich. However, some significant differences are, observed between the Flavobacterium and human structures. The active site, of Flavobacterium glycosylasparaginase is in an open conformation when, compared ... | Glycosylasparaginase (GA) is a member of a novel family of N-terminal, nucleophile hydrolases that catalytically use an N-terminal residue as, both a polarizing base and a nucleophile. These enzymes are activated from, a single chain precursor by intramolecular autoproteolysis to yield the, N-terminal nucleophile. A deficiency of GA results in the human genetic, disorder known as aspartylglycosaminuria. In this study, we report the, crystal structure of recombinant GA from Flavobacterium meningosepticum., Similar to the human structure, the bacterial GA forms an, alphabetabetaalpha sandwich. However, some significant differences are, observed between the Flavobacterium and human structures. The active site, of Flavobacterium glycosylasparaginase is in an open conformation when, compared with the human structure. We also describe the structure of a, mutant wherein the N-terminal nucleophile Thr152 is substituted by a, cysteine. In the bacterial GA crystals, we observe a heterotetrameric, structure similar to that found in the human structure, as well as that, observed in solution for eukaryotic glycosylasparaginases. The results, confirm the suitability of the bacterial enzyme as a model to study the, consequences of mutations in aspartylglycosaminuria patients. They also, suggest that further studies are necessary to understand the detail, mechanism of this enzyme. The presence of the heterotetrameric structure, in the crystals is significant because dimerization of precursors has been, suggested in the human enzyme to be a prerequisite to trigger, autoproteolysis. | ||
==About this Structure== | ==About this Structure== | ||
2GAW is a | 2GAW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Elizabethkingia_meningoseptica Elizabethkingia meningoseptica]. Active as [http://en.wikipedia.org/wiki/N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.26 3.5.1.26] Structure known Active Site: CAT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2GAW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: n-terminal nucleophile hydrolase]] | [[Category: n-terminal nucleophile hydrolase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:34:32 2007'' | ||
