2gaw: Difference between revisions

Revision as of 18:29, 21 February 2008

WILD TYPE GLYCOSYLASPARAGINASE FROM FLAVOBACTERIUM MENINGOSEPTICUM

OverviewOverview

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 StructureAbout this Structure

2GAW is a Protein complex structure of sequences from Elizabethkingia meningoseptica. Active as N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase, with EC number 3.5.1.26 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Crystal structures of Flavobacterium glycosylasparaginase. An N-terminal nucleophile hydrolase activated by intramolecular proteolysis., Guo HC, Xu Q, Buckley D, Guan C, J Biol Chem. 1998 Aug 7;273(32):20205-12. PMID:9685368

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OCA

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 ==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 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.
+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==
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 [[Category: N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase]]
 [[Category: Protein complex]]
-[[Category: Guo, H.C.]]
+[[Category: Guo, H C.]]
 [[Category: Xu, Q.]]
 [[Category: autoproteolysis]]
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 [[Category: n-terminal nucleophile hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:37:55 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:29:53 2008''