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1hty

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(New page: 200px<br /><applet load="1hty" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hty, resolution 1.40&Aring;" /> '''GOLGI ALPHA-MANNOSID...)
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[[Image:1hty.gif|left|200px]]<br /><applet load="1hty" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1hty, resolution 1.40&Aring;" />
 
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'''GOLGI ALPHA-MANNOSIDASE II'''<br />
 
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==Overview==
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==GOLGI ALPHA-MANNOSIDASE II==
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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.
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<StructureSection load='1hty' size='340' side='right'caption='[[1hty]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
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== Structural highlights ==
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<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>
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</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>
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<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>
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<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>
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</table>
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== Function ==
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[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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ht/1hty_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1HTY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with NAG, ZN, TRS and MRD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HTY OCA].
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*[[Mannosidase 3D structures|Mannosidase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=11406577 11406577]
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[[Category: Drosophila melanogaster]]
[[Category: Drosophila melanogaster]]
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[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Kuntz DA]]
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[[Category: Elsen, J.M.H.van.den.]]
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[[Category: Rose DR]]
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[[Category: Kuntz, D.A.]]
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[[Category: Van den Elsen JMH]]
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[[Category: Rose, D.R.]]
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[[Category: MRD]]
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[[Category: NAG]]
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[[Category: TRS]]
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[[Category: ZN]]
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[[Category: 2 c-terminal beta barrels]]
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[[Category: n-terminal alpha-beta domain]]
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[[Category: three helix bundle]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:49:39 2007''
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Current revision

GOLGI ALPHA-MANNOSIDASE II

PDB ID 1hty

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