1x9d

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[[Image:1x9d.gif|left|200px]]<br /><applet load="1x9d" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1x9d, resolution 1.410&Aring;" />
 
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'''Crystal Structure Of Human Class I alpha-1,2-Mannosidase In Complex With Thio-Disaccharide Substrate Analogue'''<br />
 
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==Overview==
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==Crystal Structure Of Human Class I alpha-1,2-Mannosidase In Complex With Thio-Disaccharide Substrate Analogue==
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<StructureSection load='1x9d' size='340' side='right'caption='[[1x9d]], [[Resolution|resolution]] 1.41&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1x9d]] 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=1X9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X9D 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]] 1.41&#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=BU1:1,4-BUTANEDIOL'>BU1</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Z5L:methyl+2-thio-alpha-D-mannopyranoside'>Z5L</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=1x9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x9d OCA], [https://pdbe.org/1x9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x9d RCSB], [https://www.ebi.ac.uk/pdbsum/1x9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x9d ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MA1B1_HUMAN MA1B1_HUMAN] Defects in MAN1B1 are the cause of mental retardation autosomal recessive type 15 (MRT15) [MIM:[https://omim.org/entry/614202 614202]. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21763484</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/MA1B1_HUMAN MA1B1_HUMAN] Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2).<ref>PMID:12090241</ref> <ref>PMID:18003979</ref>
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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/x9/1x9d_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1x9d ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Quality control in the endoplasmic reticulum (ER) determines the fate of newly synthesized glycoproteins toward either correct folding or disposal by ER-associated degradation. Initiation of the disposal process involves selective trimming of N-glycans attached to misfolded glycoproteins by ER alpha-mannosidase I and subsequent recognition by the ER degradation-enhancing alpha-mannosidase-like protein family of lectins, both members of glycosylhydrolase family 47. The unusual inverting hydrolytic mechanism catalyzed by members of this family is investigated here by a combination of kinetic and binding analyses of wild type and mutant forms of human ER alpha-mannosidase I as well as by structural analysis of a co-complex with an uncleaved thiodisaccharide substrate analog. These data reveal the roles of potential catalytic acid and base residues and the identification of a novel (3)S(1) sugar conformation for the bound substrate analog. The co-crystal structure described here, in combination with the (1)C(4) conformation of a previously identified co-complex with the glycone mimic, 1-deoxymannojirimycin, indicates that glycoside bond cleavage proceeds through a least motion conformational twist of a properly predisposed substrate in the -1 subsite. A novel (3)H(4) conformation is proposed as the exploded transition state.
Quality control in the endoplasmic reticulum (ER) determines the fate of newly synthesized glycoproteins toward either correct folding or disposal by ER-associated degradation. Initiation of the disposal process involves selective trimming of N-glycans attached to misfolded glycoproteins by ER alpha-mannosidase I and subsequent recognition by the ER degradation-enhancing alpha-mannosidase-like protein family of lectins, both members of glycosylhydrolase family 47. The unusual inverting hydrolytic mechanism catalyzed by members of this family is investigated here by a combination of kinetic and binding analyses of wild type and mutant forms of human ER alpha-mannosidase I as well as by structural analysis of a co-complex with an uncleaved thiodisaccharide substrate analog. These data reveal the roles of potential catalytic acid and base residues and the identification of a novel (3)S(1) sugar conformation for the bound substrate analog. The co-crystal structure described here, in combination with the (1)C(4) conformation of a previously identified co-complex with the glycone mimic, 1-deoxymannojirimycin, indicates that glycoside bond cleavage proceeds through a least motion conformational twist of a properly predisposed substrate in the -1 subsite. A novel (3)H(4) conformation is proposed as the exploded transition state.
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==About this Structure==
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Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control.,Karaveg K, Siriwardena A, Tempel W, Liu ZJ, Glushka J, Wang BC, Moremen KW J Biol Chem. 2005 Apr 22;280(16):16197-207. Epub 2005 Feb 15. PMID:15713668<ref>PMID:15713668</ref>
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1X9D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=SMD:'>SMD</scene> and <scene name='pdbligand=BU1:'>BU1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,2-alpha-mannosidase Mannosyl-oligosaccharide 1,2-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.113 3.2.1.113] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X9D OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control., Karaveg K, Siriwardena A, Tempel W, Liu ZJ, Glushka J, Wang BC, Moremen KW, J Biol Chem. 2005 Apr 22;280(16):16197-207. Epub 2005 Feb 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15713668 15713668]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 1x9d" style="background-color:#fffaf0;"></div>
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[[Category: Mannosyl-oligosaccharide 1,2-alpha-mannosidase]]
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[[Category: Single protein]]
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[[Category: Karaveg, K.]]
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[[Category: Liu, Z J.]]
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[[Category: Moremen, K W.]]
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[[Category: Siriwardena, A.]]
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[[Category: Tempel, W.]]
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[[Category: Wang, B C.]]
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[[Category: BU1]]
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[[Category: CA]]
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[[Category: SMD]]
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[[Category: SO4]]
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[[Category: glycosyl hydrolase]]
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[[Category: mannosidase]]
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[[Category: substrate analogue]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:52:22 2008''
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==See Also==
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*[[Mannosidase 3D structures|Mannosidase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Karaveg K]]
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[[Category: Liu ZJ]]
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[[Category: Moremen KW]]
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[[Category: Siriwardena A]]
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[[Category: Tempel W]]
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[[Category: Wang BC]]

Current revision

Crystal Structure Of Human Class I alpha-1,2-Mannosidase In Complex With Thio-Disaccharide Substrate Analogue

PDB ID 1x9d

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