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| | ==Crystal structure of a mutant glycosylasparaginase (G172D) that causes the genetic disease Aspartylglucosaminuria== | | ==Crystal structure of a mutant glycosylasparaginase (G172D) that causes the genetic disease Aspartylglucosaminuria== |
| - | <StructureSection load='5v2i' size='340' side='right' caption='[[5v2i]], [[Resolution|resolution]] 1.83Å' scene=''> | + | <StructureSection load='5v2i' size='340' side='right'caption='[[5v2i]], [[Resolution|resolution]] 1.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v2i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_13253 Atcc 13253]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V2I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v2i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Elizabethkingia_meningoseptica Elizabethkingia meningoseptica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V2I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V2I FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BES09_04975 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=238 ATCC 13253])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.83Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v2i OCA], [http://pdbe.org/5v2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v2i RCSB], [http://www.ebi.ac.uk/pdbsum/5v2i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v2i ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5v2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v2i OCA], [https://pdbe.org/5v2i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v2i RCSB], [https://www.ebi.ac.uk/pdbsum/5v2i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v2i ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ASPG_ELIMR ASPG_ELIMR] Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins. Requires that the glycosylated asparagine moiety is not substituted on its N-(R1) and C- (R2) terminus. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5v2i" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5v2i" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Asparaginase 3D structures|Asparaginase 3D structures]] |
| | + | *[[Glycosylasparaginase|Glycosylasparaginase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 13253]] | + | [[Category: Elizabethkingia meningoseptica]] |
| - | [[Category: Guo, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Pande, S]] | + | [[Category: Guo H]] |
| - | [[Category: Beta-aha]] | + | [[Category: Pande S]] |
| - | [[Category: Catalytic mechanism]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
ASPG_ELIMR Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins. Requires that the glycosylated asparagine moiety is not substituted on its N-(R1) and C- (R2) terminus.
Publication Abstract from PubMed
Glycosylasparaginase (GA) is an amidase that cleaves Asn-linked glycoproteins in lysosomes. Deficiency of this enzyme causes accumulation of glycoasparagines in lysosomes of cells, resulting in a genetic condition called aspartylglycosaminuria (AGU). To better understand the mechanism of a disease-causing mutation with a single residue change from a glycine to an aspartic acid, we generated a model mutant enzyme at the corresponding position (named G172D mutant). Here we report a 1.8A resolution crystal structure of mature G172D mutant and analyzed the reason behind its low hydrolase activity. Comparison of mature G172D and wildtype GA models reveals that the presence of Asp 172 near the catalytic site affects substrate catabolism in mature G172D, making it less efficient in substrate processing. Also recent studies suggest that GA is capable of processing substrates that lack a chitobiose (Glycan, N-acetylchiobios, NAcGlc) moiety, by its exo-hydrolase activity. The mechanism for this type of catalysis is not yet clear. l-Aspartic acid beta-hydroxamate (beta-AHA) is a non-chitobiose substrate that is known to interact with GA. To study the underlying mechanism of non-chitobiose substrate processing, we built a GA-beta-AHA complex structure by comparing to a previously published G172D mutant precursor in complex with a beta-AHA molecule. A hydrolysis mechanism of beta-AHA by GA is proposed based on this complex model.
Crystal structure of a mutant glycosylasparaginase shedding light on aspartylglycosaminuria-causing mechanism as well as on hydrolysis of non-chitobiose substrate.,Pande S, Lakshminarasimhan D, Guo HC Mol Genet Metab. 2017 Apr 19. pii: S1096-7192(17)30169-5. doi:, 10.1016/j.ymgme.2017.04.008. PMID:28457719[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pande S, Lakshminarasimhan D, Guo HC. Crystal structure of a mutant glycosylasparaginase shedding light on aspartylglycosaminuria-causing mechanism as well as on hydrolysis of non-chitobiose substrate. Mol Genet Metab. 2017 Apr 19. pii: S1096-7192(17)30169-5. doi:, 10.1016/j.ymgme.2017.04.008. PMID:28457719 doi:http://dx.doi.org/10.1016/j.ymgme.2017.04.008
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