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[[Image:1hty.gif|left|200px]]


{{Structure
==GOLGI ALPHA-MANNOSIDASE II==
|PDB= 1hty |SIZE=350|CAPTION= <scene name='initialview01'>1hty</scene>, resolution 1.40&Aring;
<StructureSection load='1hty' size='340' side='right'caption='[[1hty]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene> and <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>
<table><tr><td colspan='2'>[[1hty]] 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=1HTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HTY FirstGlance]. <br>
|ACTIVITY= [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]
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
|GENE=
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=1hty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hty OCA], [https://pdbe.org/1hty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hty RCSB], [https://www.ebi.ac.uk/pdbsum/1hty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hty 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/ht/1hty_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=1hty ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Golgi alpha-mannosidase II, a key enzyme in N-glycan processing, is a target in the development of anti- cancer therapies. The crystal structure of Drosophila Golgi alpha-mannosidase II in the absence and presence of the anti-cancer agent swainsonine and the inhibitor deoxymannojirimycin reveals a novel protein fold with an active site zinc intricately involved both in the substrate specificity of the enzyme and directly in the catalytic mechanism. Identification of a putative GlcNAc binding pocket in the vicinity of the active site cavity provides a model for the binding of the GlcNAcMan(5)GlcNAc(2) substrate and the consecutive hydrolysis of the alpha1,6- and alpha1,3-linked mannose residues. The enzyme-inhibitor interactions observed provide insight into the catalytic mechanism, opening the door to the design of novel inhibitors of alpha-mannosidase II.


'''GOLGI ALPHA-MANNOSIDASE II'''
Structure of Golgi alpha-mannosidase II: a target for inhibition of growth and metastasis of cancer cells.,van den Elsen JM, Kuntz DA, Rose DR EMBO J. 2001 Jun 15;20(12):3008-17. PMID:11406577<ref>PMID:11406577</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1hty" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
Golgi alpha-mannosidase II, a key enzyme in N-glycan processing, is a target in the development of anti- cancer therapies. The crystal structure of Drosophila Golgi alpha-mannosidase II in the absence and presence of the anti-cancer agent swainsonine and the inhibitor deoxymannojirimycin reveals a novel protein fold with an active site zinc intricately involved both in the substrate specificity of the enzyme and directly in the catalytic mechanism. Identification of a putative GlcNAc binding pocket in the vicinity of the active site cavity provides a model for the binding of the GlcNAcMan(5)GlcNAc(2) substrate and the consecutive hydrolysis of the alpha1,6- and alpha1,3-linked mannose residues. The enzyme-inhibitor interactions observed provide insight into the catalytic mechanism, opening the door to the design of novel inhibitors of alpha-mannosidase II.
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1HTY is a [[Single protein]] structure of 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=1HTY OCA].
__TOC__
 
</StructureSection>
==Reference==
Structure of Golgi alpha-mannosidase II: a target for inhibition of growth and metastasis of cancer cells., van den Elsen JM, Kuntz DA, Rose DR, EMBO J. 2001 Jun 15;20(12):3008-17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11406577 11406577]
[[Category: Drosophila melanogaster]]
[[Category: Drosophila melanogaster]]
[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Kuntz DA]]
[[Category: Elsen, J M.H van den.]]
[[Category: Rose DR]]
[[Category: Kuntz, D A.]]
[[Category: Van den Elsen JMH]]
[[Category: Rose, D R.]]
[[Category: MRD]]
[[Category: NAG]]
[[Category: TRS]]
[[Category: ZN]]
[[Category: 2 c-terminal beta barrel]]
[[Category: n-terminal alpha-beta domain]]
[[Category: three helix bundle]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:41:32 2008''

Latest revision as of 06:43, 30 October 2024

GOLGI ALPHA-MANNOSIDASE II

1hty, resolution 1.40Å

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