View source for 3buq


==Golgi alpha-mannosidase II D204A catalytic nucleophile mutant with bound mannose.==
<StructureSection load='3buq' size='340' side='right' caption='[[3buq]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3buq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BUQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BUQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hty|1hty]], [[1hww|1hww]], [[1hxk|1hxk]], [[1ps2|1ps2]], [[1qwn|1qwn]], [[1qwu|1qwu]], [[1qx1|1qx1]], [[1r33|1r33]], [[1r34|1r34]], [[1tqs|1tqs]], [[1tqt|1tqt]], [[1tqu|1tqu]], [[1tqv|1tqv]], [[1tqw|1tqw]], [[2alw|2alw]], [[2f18|2f18]], [[2f1a|2f1a]], [[2f1b|2f1b]], [[2f7o|2f7o]], [[2f7p|2f7p]], [[2f7q|2f7q]], [[2f7r|2f7r]], [[3bub|3bub]], [[3bud|3bud]], [[3bui|3bui]], [[3bup|3bup]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alpha-Man-II, GmII ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,3-1,6-alpha-mannosidase Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.114 3.2.1.114] </span></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=3buq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3buq OCA], [http://pdbe.org/3buq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3buq RCSB], [http://www.ebi.ac.uk/pdbsum/3buq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3buq ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/MAN2_DROME MAN2_DROME]] Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway (By similarity). 
== 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/bu/3buq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3buq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibition of Golgi alpha-mannosidase II (GMII), which acts late in the N-glycan processing pathway, provides a route to blocking cancer-induced changes in cell surface oligosaccharide structures. To probe the substrate requirements of GMII, oligosaccharides were synthesized that contained an alpha(1,3)- or alpha(1,6)-linked 1-thiomannoside. Surprisingly, these oligosaccharides were not observed in X-ray crystal structures of native Drosophila GMII (dGMII). However, a mutant enzyme in which the catalytic nucleophilic aspartate was changed to alanine (D204A) allowed visualization of soaked oligosaccharides and led to the identification of the binding site for the alpha(1,3)-linked mannoside of the natural substrate. These studies also indicate that the conformational change of the bound mannoside to a high-energy B 2,5 conformation is facilitated by steric hindrance from, and the formation of strong hydrogen bonds to, Asp204. The observation that 1-thio-linked mannosides are not well tolerated by the catalytic site of dGMII led to the synthesis of a pentasaccharide containing the alpha(1,6)-linked Man of the natural substrate and the beta(1,2)-linked GlcNAc moiety proposed to be accommodated by the extended binding site of the enzyme. A cocrystal structure of this compound with the D204A enzyme revealed the molecular interactions with the beta(1,2)-linked GlcNAc. The structure is consistent with the approximately 80-fold preference of dGMII for the cleavage of substrates containing a nonreducing beta(1,2)-linked GlcNAc. By contrast, the lysosomal mannosidase lacks an equivalent GlcNAc binding site and kinetic analysis indicates oligomannoside substrates without non-reducing-terminal GlcNAc modifications are preferred, suggesting that selective inhibitors for GMII could exploit the additional binding specificity of the GlcNAc binding site.

Probing the Substrate Specificity of Golgi alpha-Mannosidase II by Use of Synthetic Oligosaccharides and a Catalytic Nucleophile Mutant.,Zhong W, Kuntz DA, Ember B, Singh H, Moremen KW, Rose DR, Boons GJ J Am Chem Soc. 2008 Jun 18;. PMID:18558690<ref>PMID:18558690</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3buq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]]
[[Category: Kuntz, D A]]
[[Category: Rose, D R]]
[[Category: Glycosidase]]
[[Category: Glycosyl hydrolase family 38]]
[[Category: Golgi apparatus]]
[[Category: Hydrolase]]
[[Category: Membrane]]
[[Category: Signal-anchor]]
[[Category: Transmembrane]]