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| | ==Crystal structure of the inactive state of the Smase I, a sphingomyelinase D from Loxosceles laeta venom== | | ==Crystal structure of the inactive state of the Smase I, a sphingomyelinase D from Loxosceles laeta venom== |
| - | <StructureSection load='2f9r' size='340' side='right' caption='[[2f9r]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='2f9r' size='340' side='right'caption='[[2f9r]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2f9r]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Loxla Loxla]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F9R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2F9R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2f9r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Loxosceles_laeta Loxosceles laeta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F9R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xx1|1xx1]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sphingomyelin_phosphodiesterase_D Sphingomyelin phosphodiesterase D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.41 3.1.4.41] </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=2f9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f9r OCA], [https://pdbe.org/2f9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f9r RCSB], [https://www.ebi.ac.uk/pdbsum/2f9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f9r ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f9r OCA], [http://pdbe.org/2f9r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f9r RCSB], [http://www.ebi.ac.uk/pdbsum/2f9r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2f9r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A311_LOXLA A311_LOXLA]] Catalyzes the hydrolysis of sphingomyelin. May also acts on other phosphatidyl esters. Induces complement-dependent hemolysis and dermonecrosis.<ref>PMID:12419302</ref> | + | [https://www.uniprot.org/uniprot/A311_LOXLA A311_LOXLA] Catalyzes the hydrolysis of sphingomyelin. May also acts on other phosphatidyl esters. Induces complement-dependent hemolysis and dermonecrosis.<ref>PMID:12419302</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f9/2f9r_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f9/2f9r_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Loxla]] | + | [[Category: Large Structures]] |
| - | [[Category: Sphingomyelin phosphodiesterase D]] | + | [[Category: Loxosceles laeta]] |
| - | [[Category: Arni, R K]] | + | [[Category: Arni RK]] |
| - | [[Category: Betzel, C]] | + | [[Category: Betzel C]] |
| - | [[Category: Fernandes-Pedrosa, M F]] | + | [[Category: Fernandes-Pedrosa MF]] |
| - | [[Category: Gabdoulkhakov, A]] | + | [[Category: Gabdoulkhakov A]] |
| - | [[Category: Murakami, M T]] | + | [[Category: Murakami MT]] |
| - | [[Category: Tambourgi, D V]] | + | [[Category: Tambourgi DV]] |
| - | [[Category: Catalytic activity]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inactive state]]
| + | |
| - | [[Category: Magnesium-binding site]]
| + | |
| - | [[Category: Sphingomyelinase d]]
| + | |
| Structural highlights
Function
A311_LOXLA Catalyzes the hydrolysis of sphingomyelin. May also acts on other phosphatidyl esters. Induces complement-dependent hemolysis and dermonecrosis.[1]
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
Sphingomyelinases D (SMases D) from Loxosceles spider venom are the principal toxins responsible for the manifestation of dermonecrosis, intravascular hemolysis, and acute renal failure, which can result in death. These enzymes catalyze the hydrolysis of sphingomyelin, resulting in the formation of ceramide 1-phosphate and choline or the hydrolysis of lysophosphatidyl choline, generating the lipid mediator lysophosphatidic acid. This report represents the first crystal structure of a member of the sphingomyelinase D family from Loxosceles laeta (SMase I), which has been determined at 1.75-angstrom resolution using the "quick cryo-soaking" technique and phases obtained from a single iodine derivative and data collected from a conventional rotating anode x-ray source. SMase I folds as an (alpha/beta)8 barrel, the interfacial and catalytic sites encompass hydrophobic loops and a negatively charged surface. Substrate binding and/or the transition state are stabilized by a Mg2+ ion, which is coordinated by Glu32, Asp34, Asp91, and solvent molecules. In the proposed acid base catalytic mechanism, His12 and His47 play key roles and are supported by a network of hydrogen bonds between Asp34, Asp52, Trp230, Asp233, and Asn252.
Structural basis for metal ion coordination and the catalytic mechanism of sphingomyelinases D.,Murakami MT, Fernandes-Pedrosa MF, Tambourgi DV, Arni RK J Biol Chem. 2005 Apr 8;280(14):13658-64. Epub 2005 Jan 14. PMID:15654080[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fernandes Pedrosa Mde F, Junqueira de Azevedo Ide L, Goncalves-de-Andrade RM, van den Berg CW, Ramos CR, Ho PL, Tambourgi DV. Molecular cloning and expression of a functional dermonecrotic and haemolytic factor from Loxosceles laeta venom. Biochem Biophys Res Commun. 2002 Nov 15;298(5):638-45. PMID:12419302
- ↑ Murakami MT, Fernandes-Pedrosa MF, Tambourgi DV, Arni RK. Structural basis for metal ion coordination and the catalytic mechanism of sphingomyelinases D. J Biol Chem. 2005 Apr 8;280(14):13658-64. Epub 2005 Jan 14. PMID:15654080 doi:http://dx.doi.org/10.1074/jbc.M412437200
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