2gl9: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
(12 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2gl9.gif|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_2gl9", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_2gl9|  PDB=2gl9  |  SCENE=  }}
'''Crystal Structure of Glycosylasparaginase-Substrate Complex'''


==Crystal Structure of Glycosylasparaginase-Substrate Complex==
<StructureSection load='2gl9' size='340' side='right'caption='[[2gl9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2gl9]] is a 4 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=2GL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GL9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASN:ASPARAGINE'>ASN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=2gl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl9 OCA], [https://pdbe.org/2gl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gl9 RCSB], [https://www.ebi.ac.uk/pdbsum/2gl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gl9 ProSAT]</span></td></tr>
</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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gl/2gl9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gl9 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glycosylasparaginase (GA) plays an important role in asparagine-linked glycoprotein degradation. A deficiency in the activity of human GA leads to a lysosomal storage disease named aspartylglycosaminuria. GA belongs to a superfamily of N-terminal nucleophile hydrolases that autoproteolytically generate their mature enzymes from inactive single chain protein precursors. The side-chain of the newly exposed N-terminal residue then acts as a nucleophile during substrate hydrolysis. By taking advantage of mutant enzyme of Flavobacterium meningosepticum GA with reduced enzymatic activity, we have obtained a crystallographic snapshot of a productive complex with its substrate (NAcGlc-Asn), at 2.0 A resolution. This complex structure provided us an excellent model for the Michaelis complex to examine the specific contacts critical for substrate binding and catalysis. Substrate binding induces a conformational change near the active site of GA. To initiate catalysis, the side-chain of the N-terminal Thr152 is polarized by the free alpha-amino group on the same residue, mediated by the side-chain hydroxyl group of Thr170. Cleavage of the amide bond is then accomplished by a nucleophilic attack at the carbonyl carbon of the amide linkage in the substrate, leading to the formation of an acyl-enzyme intermediate through a negatively charged tetrahedral transition state.


==Overview==
Crystallographic snapshot of a productive glycosylasparaginase-substrate complex.,Wang Y, Guo HC J Mol Biol. 2007 Feb 9;366(1):82-92. Epub 2006 Sep 26. PMID:17157318<ref>PMID:17157318</ref>
Glycosylasparaginase (GA) plays an important role in asparagine-linked glycoprotein degradation. A deficiency in the activity of human GA leads to a lysosomal storage disease named aspartylglycosaminuria. GA belongs to a superfamily of N-terminal nucleophile hydrolases that autoproteolytically generate their mature enzymes from inactive single chain protein precursors. The side-chain of the newly exposed N-terminal residue then acts as a nucleophile during substrate hydrolysis. By taking advantage of mutant enzyme of Flavobacterium meningosepticum GA with reduced enzymatic activity, we have obtained a crystallographic snapshot of a productive complex with its substrate (NAcGlc-Asn), at 2.0 A resolution. This complex structure provided us an excellent model for the Michaelis complex to examine the specific contacts critical for substrate binding and catalysis. Substrate binding induces a conformational change near the active site of GA. To initiate catalysis, the side-chain of the N-terminal Thr152 is polarized by the free alpha-amino group on the same residue, mediated by the side-chain hydroxyl group of Thr170. Cleavage of the amide bond is then accomplished by a nucleophilic attack at the carbonyl carbon of the amide linkage in the substrate, leading to the formation of an acyl-enzyme intermediate through a negatively charged tetrahedral transition state.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2GL9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Elizabethkingia_meningoseptica Elizabethkingia meningoseptica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GL9 OCA].
</div>
<div class="pdbe-citations 2gl9" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystallographic snapshot of a productive glycosylasparaginase-substrate complex., Wang Y, Guo HC, J Mol Biol. 2007 Feb 9;366(1):82-92. Epub 2006 Sep 26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17157318 17157318]
*[[Asparaginase 3D structures|Asparaginase 3D structures]]
*[[Glycosylasparaginase|Glycosylasparaginase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Elizabethkingia meningoseptica]]
[[Category: Elizabethkingia meningoseptica]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Guo, H C.]]
[[Category: Guo HC]]
[[Category: Wang, Y.]]
[[Category: Wang Y]]
[[Category: Catalytic mechanism]]
[[Category: Crystal structure]]
[[Category: Electron-pair transfer]]
[[Category: Enzyme-acyl intermediate]]
[[Category: Enzyme-substrate complex]]
[[Category: Glycosylasparaginase]]
[[Category: Ntn-hydrolase]]
[[Category: Nucleophilic attack]]
[[Category: Oxyanion hole]]
[[Category: Proton-relay network]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:13:46 2008''
Retrieved from "https://proteopedia.org/2gl9"