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| | <StructureSection load='3rlh' size='340' side='right'caption='[[3rlh]], [[Resolution|resolution]] 1.72Å' scene=''> | | <StructureSection load='3rlh' size='340' side='right'caption='[[3rlh]], [[Resolution|resolution]] 1.72Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rlh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Brown_spider Brown spider]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RLH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rlh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Loxosceles_intermedia Loxosceles intermedia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RLH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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]] 1.72Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rlg|3rlg]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Sphingomyelin_phosphodiesterase_D Sphingomyelin phosphodiesterase D], with EC number [https://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=3rlh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rlh OCA], [https://pdbe.org/3rlh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rlh RCSB], [https://www.ebi.ac.uk/pdbsum/3rlh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rlh 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=3rlh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rlh OCA], [https://pdbe.org/3rlh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rlh RCSB], [https://www.ebi.ac.uk/pdbsum/3rlh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rlh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/A1HA_LOXIN A1HA_LOXIN]] Catalyzes the hydrolysis of sphingomyelin, lysophosphatidylcholine, and lyso-platelet activating factor but not that of phosphatidylcholine. Shows a high enzymatic activity. Induces dermonecrosis, blood vessel permeability and platelet aggregation (PubMed:9790962). Is directly toxic to kidney (PubMed:16005484) and liver (PubMed:18765244). Also induces hemolysis in a complement-dependent manner (PubMed:9790962) as well as in a complement-independent manner. The hemolysis provoked in a complement-independent manner is composed of several steps. The toxin binds to erythrocyte membranes, hydrolyzes membrane phospholipids (sphingomyelin and lysophosphatidylcholine) thus generating metabolism products that cause hemolysis, probably by provoking an increase of calcium inside cells. The calcium influx is due to the opening of L-type calcium channels, since L-type calcium channel blockers inhibit calcium influx (PubMed:21590705).<ref>PMID:16005484</ref> <ref>PMID:18760322</ref> <ref>PMID:18765244</ref> <ref>PMID:19455508</ref> <ref>PMID:21590705</ref> <ref>PMID:9790962</ref>
| + | [https://www.uniprot.org/uniprot/A1HA_LOXIN A1HA_LOXIN] Catalyzes the hydrolysis of sphingomyelin, lysophosphatidylcholine, and lyso-platelet activating factor but not that of phosphatidylcholine. Shows a high enzymatic activity. Induces dermonecrosis, blood vessel permeability and platelet aggregation (PubMed:9790962). Is directly toxic to kidney (PubMed:16005484) and liver (PubMed:18765244). Also induces hemolysis in a complement-dependent manner (PubMed:9790962) as well as in a complement-independent manner. The hemolysis provoked in a complement-independent manner is composed of several steps. The toxin binds to erythrocyte membranes, hydrolyzes membrane phospholipids (sphingomyelin and lysophosphatidylcholine) thus generating metabolism products that cause hemolysis, probably by provoking an increase of calcium inside cells. The calcium influx is due to the opening of L-type calcium channels, since L-type calcium channel blockers inhibit calcium influx (PubMed:21590705).<ref>PMID:16005484</ref> <ref>PMID:18760322</ref> <ref>PMID:18765244</ref> <ref>PMID:19455508</ref> <ref>PMID:21590705</ref> <ref>PMID:9790962</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Phospholipases D (PLDs) are principally responsible for the local and systemic effects of Loxosceles envenomation including dermonecrosis and hemolysis. Despite their clinical relevance in loxoscelism, to date, only the SMase I from Loxosceles laeta, a class I member, has been structurally characterized. The crystal structure of a class II member from Loxosceles intermedia venom has been determined at 1.7A resolution. Structural comparison to the class I member showed that the presence of an additional disulphide bridge which links the catalytic loop to the flexible loop significantly changes the volume and shape of the catalytic cleft. An examination of the crystal structures of PLD homologues in the presence of low molecular weight compounds at their active sites suggests the existence of a ligand-dependent rotamer conformation of the highly conserved residue Trp230 (equivalent to Trp192 in the glycerophosphodiester phosphodiesterase from Thermus thermophofilus, PDB code: 1VD6) indicating its role in substrate binding in both enzymes. Sequence and structural analyses suggest that the reduced sphingomyelinase activity observed in some class IIb PLDs is probably due to point mutations which lead to a different substrate preference.
| + | |
| - | | + | |
| - | Structure of a novel class II phospholipase D: Catalytic cleft is modified by a disulphide bridge.,de Giuseppe PO, Ullah A, Silva DT, Gremski LH, Wille AC, Chaves Moreira D, Ribeiro AS, Chaim OM, Murakami MT, Veiga SS, Arni RK Biochem Biophys Res Commun. 2011 Jun 17;409(4):622-7. Epub 2011 May 17. PMID:21616057<ref>PMID:21616057</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3rlh" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Phospholipase D|Phospholipase D]] | + | *[[Phospholipase D 3D structures|Phospholipase D 3D structures]] |
| | *[[Sphingomyelinase|Sphingomyelinase]] | | *[[Sphingomyelinase|Sphingomyelinase]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brown spider]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Sphingomyelin phosphodiesterase D]] | + | [[Category: Loxosceles intermedia]] |
| - | [[Category: Arni, R K]] | + | [[Category: Arni RK]] |
| - | [[Category: Giuseppe, P O]] | + | [[Category: Giuseppe PO]] |
| - | [[Category: Murakami, M T]] | + | [[Category: Murakami MT]] |
| - | [[Category: Ullah, A]] | + | [[Category: Ullah A]] |
| - | [[Category: Veiga, S S]] | + | [[Category: Veiga SS]] |
| - | [[Category: Class ii pld]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phospholipase d]]
| + | |
| - | [[Category: Plc-like phosphodiesterase]]
| + | |
| - | [[Category: Tim beta/alpha-barrel superfamily]]
| + | |
| - | [[Category: Venom]]
| + | |
| Structural highlights
Function
A1HA_LOXIN Catalyzes the hydrolysis of sphingomyelin, lysophosphatidylcholine, and lyso-platelet activating factor but not that of phosphatidylcholine. Shows a high enzymatic activity. Induces dermonecrosis, blood vessel permeability and platelet aggregation (PubMed:9790962). Is directly toxic to kidney (PubMed:16005484) and liver (PubMed:18765244). Also induces hemolysis in a complement-dependent manner (PubMed:9790962) as well as in a complement-independent manner. The hemolysis provoked in a complement-independent manner is composed of several steps. The toxin binds to erythrocyte membranes, hydrolyzes membrane phospholipids (sphingomyelin and lysophosphatidylcholine) thus generating metabolism products that cause hemolysis, probably by provoking an increase of calcium inside cells. The calcium influx is due to the opening of L-type calcium channels, since L-type calcium channel blockers inhibit calcium influx (PubMed:21590705).[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Chaim OM, Sade YB, da Silveira RB, Toma L, Kalapothakis E, Chavez-Olortegui C, Mangili OC, Gremski W, von Dietrich CP, Nader HB, Sanches Veiga S. Brown spider dermonecrotic toxin directly induces nephrotoxicity. Toxicol Appl Pharmacol. 2006 Feb 15;211(1):64-77. Epub 2005 Jul 11. PMID:16005484 doi:http://dx.doi.org/S0041-008X(05)00361-3
- ↑ Kusma J, Chaim OM, Wille AC, Ferrer VP, Sade YB, Donatti L, Gremski W, Mangili OC, Veiga SS. Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity. Biochimie. 2008 Nov-Dec;90(11-12):1722-36. doi: 10.1016/j.biochi.2008.07.011., Epub 2008 Aug 9. PMID:18760322 doi:http://dx.doi.org/10.1016/j.biochi.2008.07.011
- ↑ de Oliveira Christoff A, de Oliveira A, Chaim OM, Lugarini D, Bastos Pereira AL, Paludo KS, Queiroz Telles JE, Bracht A, Veiga SS, Acco A. Effects of the venom and the dermonecrotic toxin LiRecDT1 of Loxosceles intermedia in the rat liver. Toxicon. 2008 Nov;52(6):695-704. Epub 2008 Aug 13. PMID:18765244 doi:http://dx.doi.org/S0041-0101(08)00457-1
- ↑ Chaves-Moreira D, Chaim OM, Sade YB, Paludo KS, Gremski LH, Donatti L, de Moura J, Mangili OC, Gremski W, da Silveira RB, Senff-Ribeiro A, Veiga SS. Identification of a direct hemolytic effect dependent on the catalytic activity induced by phospholipase-D (dermonecrotic toxin) from brown spider venom. J Cell Biochem. 2009 Jul 1;107(4):655-66. doi: 10.1002/jcb.22148. PMID:19455508 doi:http://dx.doi.org/10.1002/jcb.22148
- ↑ Chaves-Moreira D, Souza FN, Fogaca RT, Mangili OC, Gremski W, Senff-Ribeiro A, Chaim OM, Veiga SS. The relationship between calcium and the metabolism of plasma membrane phospholipids in hemolysis induced by brown spider venom phospholipase-D toxin. J Cell Biochem. 2011 Sep;112(9):2529-40. doi: 10.1002/jcb.23177. PMID:21590705 doi:http://dx.doi.org/10.1002/jcb.23177
- ↑ Tambourgi DV, Magnoli FC, van den Berg CW, Morgan BP, de Araujo PS, Alves EW, Da Silva WD. Sphingomyelinases in the venom of the spider Loxosceles intermedia are responsible for both dermonecrosis and complement-dependent hemolysis. Biochem Biophys Res Commun. 1998 Oct 9;251(1):366-73. PMID:9790962 doi:http://dx.doi.org/S0006-291X(98)99474-8
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