1o7d

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[[Image:1o7d.jpg|left|200px]]<br /><applet load="1o7d" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1o7d, resolution 2.70&Aring;" />
 
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'''THE STRUCTURE OF THE BOVINE LYSOSOMAL A-MANNOSIDASE SUGGESTS A NOVEL MECHANISM FOR LOW PH ACTIVATION'''<br />
 
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==Overview==
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==The structure of the bovine lysosomal a-mannosidase suggests a novel mechanism for low pH activation==
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Lysosomal alpha-mannosidase (LAM: EC 3.2.1.24) belongs to the, sequence-based glycoside hydrolase family 38 (GH38). Two other mammalian, GH38 members, Golgi alpha-mannosidase II (GIIAM) and cytosolic, alpha-mannosidase, are expressed in all tissues. In humans, cattle, cat, and guinea pig, lack of lysosomal alpha-mannosidase activity causes the, autosomal recessive disease alpha-mannosidosis. Here, we describe the, three-dimensional structure of bovine lysosomal alpha-mannosidase (bLAM), at 2.7A resolution and confirm the solution state dimer by electron, microscopy. We present the first structure of a mammalian GH38 enzyme that, offers indications for the signal areas for mannose phosphorylation, suggests a previously undetected mechanism of low-pH activation and, provides a template for further biochemical studies of the family 38, glycoside hydrolases as well as lysosomal transport. Furthermore, it, provides a basis for understanding the human form of alpha-mannosidosis at, the atomic level. The atomic coordinates and structure factors have been, deposited in the Protein Data Bank (accession codes 1o7d and r1o7dsf).
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<StructureSection load='1o7d' size='340' side='right'caption='[[1o7d]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1o7d]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O7D 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]] 2.7&#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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1o7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o7d OCA], [https://pdbe.org/1o7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o7d RCSB], [https://www.ebi.ac.uk/pdbsum/1o7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o7d ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MA2B1_BOVIN MA2B1_BOVIN] Note=Defects in MAN2B1 are the cause of lysosomal alpha-mannosidosis (AM). AM is a lysosomal storage disease characterized by accumulation of unbranched oligosaccharide chains. The disease manifests itself by head tremor, aggressive tendency, ataxia, failure to thrive, and early death.
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== Function ==
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[https://www.uniprot.org/uniprot/MA2B1_BOVIN MA2B1_BOVIN] Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover.
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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/o7/1o7d_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=1o7d 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 ==
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Lysosomal alpha-mannosidase (LAM: EC 3.2.1.24) belongs to the sequence-based glycoside hydrolase family 38 (GH38). Two other mammalian GH38 members, Golgi alpha-mannosidase II (GIIAM) and cytosolic alpha-mannosidase, are expressed in all tissues. In humans, cattle, cat and guinea pig, lack of lysosomal alpha-mannosidase activity causes the autosomal recessive disease alpha-mannosidosis. Here, we describe the three-dimensional structure of bovine lysosomal alpha-mannosidase (bLAM) at 2.7A resolution and confirm the solution state dimer by electron microscopy. We present the first structure of a mammalian GH38 enzyme that offers indications for the signal areas for mannose phosphorylation, suggests a previously undetected mechanism of low-pH activation and provides a template for further biochemical studies of the family 38 glycoside hydrolases as well as lysosomal transport. Furthermore, it provides a basis for understanding the human form of alpha-mannosidosis at the atomic level. The atomic coordinates and structure factors have been deposited in the Protein Data Bank (accession codes 1o7d and r1o7dsf).
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==About this Structure==
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The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation.,Heikinheimo P, Helland R, Leiros HK, Leiros I, Karlsen S, Evjen G, Ravelli R, Schoehn G, Ruigrok R, Tollersrud OK, McSweeney S, Hough E J Mol Biol. 2003 Mar 28;327(3):631-44. PMID:12634058<ref>PMID:12634058</ref>
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1O7D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=TRS:'>TRS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alpha-mannosidase Alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.24 3.2.1.24] Known structural/functional Site: <scene name='pdbsite=ACT:Zn+Binding+Site+For+Chain+A'>ACT</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O7D 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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The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation., Heikinheimo P, Helland R, Leiros HK, Leiros I, Karlsen S, Evjen G, Ravelli R, Schoehn G, Ruigrok R, Tollersrud OK, McSweeney S, Hough E, J Mol Biol. 2003 Mar 28;327(3):631-44. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12634058 12634058]
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</div>
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[[Category: Alpha-mannosidase]]
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<div class="pdbe-citations 1o7d" style="background-color:#fffaf0;"></div>
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[[Category: Bos taurus]]
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[[Category: Single protein]]
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[[Category: Evjen, G.]]
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[[Category: Heikinheimo, P.]]
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[[Category: Helland, R.]]
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[[Category: Hough, E.]]
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[[Category: Karlsen, S.]]
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[[Category: Leiros, H.S.]]
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[[Category: Leiros, I.]]
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[[Category: Mcsweeney, S.]]
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[[Category: Ravelli, R.]]
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[[Category: Ruigrok, R.]]
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[[Category: Schoehn, G.]]
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[[Category: Tollersrud, O.K.]]
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[[Category: NAG]]
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[[Category: SO4]]
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[[Category: TRS]]
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[[Category: ZN]]
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[[Category: a-mannosidase]]
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[[Category: glycosyl hydrolase family 38]]
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[[Category: lysosomal]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:54:25 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: Bos taurus]]
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[[Category: Large Structures]]
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[[Category: Evjen G]]
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[[Category: Heikinheimo P]]
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[[Category: Helland R]]
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[[Category: Hough E]]
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[[Category: Karlsen S]]
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[[Category: Leiros HS]]
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[[Category: Leiros I]]
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[[Category: Mcsweeney S]]
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[[Category: Ravelli R]]
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[[Category: Ruigrok R]]
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[[Category: Schoehn G]]
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[[Category: Tollersrud O-K]]

Current revision

The structure of the bovine lysosomal a-mannosidase suggests a novel mechanism for low pH activation

PDB ID 1o7d

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