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[[Image:1fmi.gif|left|200px]]
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{{STRUCTURE_1fmi|  PDB=1fmi  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE'''


==CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE==
<StructureSection load='1fmi' size='340' side='right'caption='[[1fmi]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fmi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FMI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FMI 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1fmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fmi OCA], [https://pdbe.org/1fmi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fmi RCSB], [https://www.ebi.ac.uk/pdbsum/1fmi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fmi ProSAT]</span></td></tr>
</table>
== 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/fm/1fmi_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=1fmi ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases.


==Overview==
Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases.,Vallee F, Karaveg K, Herscovics A, Moremen KW, Howell PL J Biol Chem. 2000 Dec 29;275(52):41287-98. PMID:10995765<ref>PMID:10995765</ref>
Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1FMI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FMI OCA].
</div>
<div class="pdbe-citations 1fmi" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases., Vallee F, Karaveg K, Herscovics A, Moremen KW, Howell PL, J Biol Chem. 2000 Dec 29;275(52):41287-98. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10995765 10995765]
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Mannosyl-oligosaccharide 1,2-alpha-mannosidase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Herscovics A]]
[[Category: Herscovics, A.]]
[[Category: Howell PL]]
[[Category: Howell, P L.]]
[[Category: Karaveg K]]
[[Category: Karaveg, K.]]
[[Category: Moremen KW]]
[[Category: Moremen, K W.]]
[[Category: Vallee F]]
[[Category: Vallee, F.]]
[[Category: Alpha-alpha7 barrel]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:30:16 2008''

Latest revision as of 23:58, 20 November 2024

CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE

1fmi, resolution 1.90Å

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