View source for 3ddg


==GOLGI MANNOSIDASE II complex with (3R,4R,5R)-3,4-Dihydroxy-5-({[(1R)-2-hydroxy-1 phenylethyl]amino}methyl) methylpyrrolidin-2-one==
<StructureSection load='3ddg' size='340' side='right'caption='[[3ddg]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ddg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DDG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DDG 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]] 1.74&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GB7:(3R,4R,5R)-3,4-DIHYDROXY-5-({[(1R)-2-HYDROXY-1-PHENYLETHYL]AMINO}METHYL)-1-METHYLPYRROLIDIN-2-ONE'>GB7</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3ddg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ddg OCA], [https://pdbe.org/3ddg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ddg RCSB], [https://www.ebi.ac.uk/pdbsum/3ddg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ddg ProSAT]</span></td></tr>
</table>
== Function ==
[https://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/dd/3ddg_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=3ddg ConSurf].
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== Publication Abstract from PubMed ==
Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi alpha-mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of alpha-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.

Functionalized pyrrolidine inhibitors of human type II alpha-mannosidases as anti-cancer agents: optimizing the fit to the active site.,Fiaux H, Kuntz DA, Hoffman D, Janzer RC, Gerber-Lemaire S, Rose DR, Juillerat-Jeanneret L Bioorg Med Chem. 2008 Aug 1;16(15):7337-46. Epub 2008 Jun 14. PMID:18599296<ref>PMID:18599296</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3ddg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Hoffman D]]
[[Category: Kuntz DA]]
[[Category: Rose DR]]