2f9r
From Proteopedia
(New page: 200px<br /><applet load="2f9r" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f9r, resolution 1.85Å" /> '''Crystal structure of...) |
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| - | [[Image:2f9r.gif|left|200px]]<br /><applet load="2f9r" size=" | + | [[Image:2f9r.gif|left|200px]]<br /><applet load="2f9r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2f9r, resolution 1.85Å" /> | caption="2f9r, resolution 1.85Å" /> | ||
'''Crystal structure of the inactive state of the Smase I, a sphingomyelinase D from Loxosceles laeta venom'''<br /> | '''Crystal structure of the inactive state of the Smase I, a sphingomyelinase D from Loxosceles laeta venom'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Sphingomyelinases D (SMases D) from Loxosceles spider venom are the | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2F9R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Loxosceles_laeta Loxosceles laeta] with MG and EPE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 2F9R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Loxosceles_laeta Loxosceles laeta] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F9R OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Sphingomyelin phosphodiesterase D]] | [[Category: Sphingomyelin phosphodiesterase D]] | ||
| - | [[Category: Arni, R | + | [[Category: Arni, R K.]] |
[[Category: Betzel, C.]] | [[Category: Betzel, C.]] | ||
| - | [[Category: Fernandes-Pedrosa, M | + | [[Category: Fernandes-Pedrosa, M F.]] |
[[Category: Gabdoulkhakov, A.]] | [[Category: Gabdoulkhakov, A.]] | ||
| - | [[Category: Murakami, M | + | [[Category: Murakami, M T.]] |
| - | [[Category: Tambourgi, D | + | [[Category: Tambourgi, D V.]] |
[[Category: EPE]] | [[Category: EPE]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: sphingomyelinase d]] | [[Category: sphingomyelinase d]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:19:10 2008'' |
Revision as of 15:19, 21 February 2008
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Crystal structure of the inactive state of the Smase I, a sphingomyelinase D from Loxosceles laeta venom
Overview
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.
About this Structure
2F9R is a Single protein structure of sequence from Loxosceles laeta with and as ligands. Active as Sphingomyelin phosphodiesterase D, with EC number 3.1.4.41 Full crystallographic information is available from OCA.
Reference
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
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