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| | <StructureSection load='2agc' size='340' side='right'caption='[[2agc]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2agc' size='340' side='right'caption='[[2agc]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2agc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AGC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2agc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AGC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1g13|1g13]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gm2a ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2agc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2agc OCA], [https://pdbe.org/2agc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2agc RCSB], [https://www.ebi.ac.uk/pdbsum/2agc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2agc ProSAT]</span></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=2agc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2agc OCA], [https://pdbe.org/2agc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2agc RCSB], [https://www.ebi.ac.uk/pdbsum/2agc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2agc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SAP3_MOUSE SAP3_MOUSE]] 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. The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity.
| + | [https://www.uniprot.org/uniprot/SAP3_MOUSE SAP3_MOUSE] 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. The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Lee, S]] | + | [[Category: Lee S]] |
| - | [[Category: Mi, L Z]] | + | [[Category: Mi LZ]] |
| - | [[Category: Rastinejad, F]] | + | [[Category: Rastinejad F]] |
| - | [[Category: Wright, C S]] | + | [[Category: Wright CS]] |
| - | [[Category: Constricted lipid binding pocket]]
| + | |
| - | [[Category: Lipid binding protein]]
| + | |
| Structural highlights
Function
SAP3_MOUSE 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. The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wright CS, Mi LZ, Lee S, Rastinejad F. Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity. Biochemistry. 2005 Oct 18;44(41):13510-21. PMID:16216074 doi:http://dx.doi.org/10.1021/bi050668w
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