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{{STRUCTURE_2ag2|  PDB=2ag2  |  SCENE=  }}
==Crystal Structure Analysis of GM2-activator protein complexed with Phosphatidylcholine==
===Crystal Structure Analysis of GM2-activator protein complexed with Phosphatidylcholine===
<StructureSection load='2ag2' size='340' side='right' caption='[[2ag2]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
{{ABSTRACT_PUBMED_16216074}}
== Structural highlights ==
 
<table><tr><td colspan='2'>[[2ag2]] is a 3 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=2AG2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AG2 FirstGlance]. <br>
==Disease==
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CH5:2-(((R)-2,3-DIHYDROXYPROPYL)PHOSPHORYLOXY)-N,N,N-TRIMETHYLETHANAMINIUM'>CH5</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=LP3:(7R)-4,7-DIHYDROXY-N,N,N-TRIMETHYL-10-OXO-3,5,9-TRIOXA-4-PHOSPHAHEPTACOSAN-1-AMINIUM+4-OXIDE'>LP3</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene><br>
[[http://www.uniprot.org/uniprot/SAP3_HUMAN SAP3_HUMAN]] Defects in GM2A are the cause of GM2-gangliosidosis type AB (GM2GAB) [MIM:[http://omim.org/entry/272750 272750]]; also known as Tay-Sachs disease AB variant. GM2-gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. GM2GAB is characterized by GM2 gangliosides accumulation in the presence of both hexosaminidase A and B.<ref>PMID:1915858</ref><ref>PMID:8244332</ref><ref>PMID:8900233</ref>  
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1g13|1g13]], [[1pub|1pub]], [[1pu5|1pu5]], [[1tjj|1tjj]]</td></tr>
 
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GM2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
==Function==
<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=2ag2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ag2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ag2 RCSB], [http://www.ebi.ac.uk/pdbsum/2ag2 PDBsum]</span></td></tr>
<table>
== Disease ==
[[http://www.uniprot.org/uniprot/SAP3_HUMAN SAP3_HUMAN]] Defects in GM2A are the cause of GM2-gangliosidosis type AB (GM2GAB) [MIM:[http://omim.org/entry/272750 272750]]; also known as Tay-Sachs disease AB variant. GM2-gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. GM2GAB is characterized by GM2 gangliosides accumulation in the presence of both hexosaminidase A and B.<ref>PMID:1915858</ref> <ref>PMID:8244332</ref> <ref>PMID:8900233</ref>
== Function ==
[[http://www.uniprot.org/uniprot/SAP3_HUMAN SAP3_HUMAN]] The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity (By similarity). Binds gangliosides and stimulates ganglioside GM2 degradation. It stimulates only the breakdown of ganglioside GM2 and glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3.  
[[http://www.uniprot.org/uniprot/SAP3_HUMAN SAP3_HUMAN]] The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity (By similarity). Binds gangliosides and stimulates ganglioside GM2 degradation. It stimulates only the breakdown of ganglioside GM2 and glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3.  
== 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/ag/2ag2_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
GM2-activator protein (GM2AP) is a lysosomal lipid transfer protein with important biological roles in ganglioside catabolism, phospholipid metabolism, and T-cell activation. Previous studies of crystal structures of GM2AP complexed with the physiological ligand GM2 and platelet activating factor (PAF) have shown binding at two specific locations within the spacious apolar pocket and an ordering effect of endogenous resident lipids. To investigate the structural basis of phospholipid binding further, GM2AP was cocrystallized with phosphatidylcholine (PC), known to interact with GM2AP. Analysis of three crystal forms revealed binding of single chain lipids and fatty acids only and surprisingly not intact PC. The regions of best defined electron density are consistent with the presence of lyso-PC and oleic acid, which constitute deacylation products of PC. Their acyl tails are in stacking contact with shorter, less well-defined stretches of electron density that may represent resident fatty acids. The GM2AP associated hydrolytic activity that generates lyso-PC was further confirmed by mass spectrometry and enzymatic assays. In addition, we report the structures of (i) mutant Y137S, assessing the role of Tyr137 in lipid transfer via the hydrophobic cleft, and (ii) apo-mouse GM2AP, revealing a hydrophobic pocket with a constricted opening. Our structural results provide new insights into the biological functions of GM2AP. The combined effect of hydrolytic and lipid transfer properties has profound implications in cellular signaling.


==About this Structure==
Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity.,Wright CS, Mi LZ, Lee S, Rastinejad F Biochemistry. 2005 Oct 18;44(41):13510-21. PMID:16216074<ref>PMID:16216074</ref>
[[2ag2]] is a 3 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=2AG2 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
<ref group="xtra">PMID:016216074</ref><ref group="xtra">PMID:011090283</ref><ref group="xtra">PMID:012909021</ref><references group="xtra"/><references/>
</div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Lee, S.]]
[[Category: Lee, S.]]

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