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1nou

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{{STRUCTURE_1nou| PDB=1nou | SCENE= }}
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==Native human lysosomal beta-hexosaminidase isoform B==
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===Native human lysosomal beta-hexosaminidase isoform B===
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<StructureSection load='1nou' size='340' side='right' caption='[[1nou]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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{{ABSTRACT_PUBMED_12662933}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nou]] is a 2 chain structure with 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=1NOU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NOU FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nou OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nou RCSB], [http://www.ebi.ac.uk/pdbsum/1nou PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/HEXB_HUMAN HEXB_HUMAN]] Defects in HEXB are the cause of GM2-gangliosidosis type 2 (GM2G2) [MIM:[http://omim.org/entry/268800 268800]]; also known as Sandhoff disease. GM2-gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. GM2G2 is clinically indistinguishable from GM2-gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula.<ref>PMID:1720305</ref> <ref>PMID:1531140</ref> <ref>PMID:8357844</ref> <ref>PMID:7626071</ref> <ref>PMID:7557963</ref> <ref>PMID:7633435</ref> <ref>PMID:8950198</ref> <ref>PMID:9401004</ref> <ref>PMID:9856491</ref> <ref>PMID:9694901</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/HEXB_HUMAN HEXB_HUMAN]] Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues.
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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/no/1nou_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/chain_selection.php?pdb_ID=2ata 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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In humans, two major beta-hexosaminidase isoenzymes exist: Hex A and Hex B. Hex A is a heterodimer of subunits alpha and beta (60% identity), whereas Hex B is a homodimer of beta-subunits. Interest in human beta-hexosaminidase stems from its association with Tay-Sachs and Sandhoff disease; these are prototypical lysosomal storage disorders resulting from the abnormal accumulation of G(M2)-ganglioside (G(M2)). Hex A degrades G(M2) by removing a terminal N-acetyl-D-galactosamine (beta-GalNAc) residue, and this activity requires the G(M2)-activator, a protein which solubilizes the ganglioside for presentation to Hex A. We present here the crystal structure of human Hex B, alone (2.4A) and in complex with the mechanistic inhibitors GalNAc-isofagomine (2.2A) or NAG-thiazoline (2.5A). From these, and the known X-ray structure of the G(M2)-activator, we have modeled Hex A in complex with the activator and ganglioside. Together, our crystallographic and modeling data demonstrate how alpha and beta-subunits dimerize to form either Hex A or Hex B, how these isoenzymes hydrolyze diverse substrates, and how many documented point mutations cause Sandhoff disease (beta-subunit mutations) and Tay-Sachs disease (alpha-subunit mutations).
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==Disease==
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Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease.,Mark BL, Mahuran DJ, Cherney MM, Zhao D, Knapp S, James MN J Mol Biol. 2003 Apr 11;327(5):1093-109. PMID:12662933<ref>PMID:12662933</ref>
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[[http://www.uniprot.org/uniprot/HEXB_HUMAN HEXB_HUMAN]] Defects in HEXB are the cause of GM2-gangliosidosis type 2 (GM2G2) [MIM:[http://omim.org/entry/268800 268800]]; also known as Sandhoff disease. GM2-gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. GM2G2 is clinically indistinguishable from GM2-gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula.<ref>PMID:1720305</ref><ref>PMID:1531140</ref><ref>PMID:8357844</ref><ref>PMID:7626071</ref><ref>PMID:7557963</ref><ref>PMID:7633435</ref><ref>PMID:8950198</ref><ref>PMID:9401004</ref><ref>PMID:9856491</ref><ref>PMID:9694901</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/HEXB_HUMAN HEXB_HUMAN]] Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues.
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</div>
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==About this Structure==
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[[1nou]] is a 2 chain structure with 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=1NOU OCA].
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==See Also==
==See Also==
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:012662933</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Beta-N-acetylhexosaminidase]]
[[Category: Beta-N-acetylhexosaminidase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]

Revision as of 15:58, 29 September 2014

Native human lysosomal beta-hexosaminidase isoform B

1nou, resolution 2.40Å

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