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| - | ==seramidase complexed with C2== | + | ==Ceramidase complexed with C2== |
| - | <StructureSection load='2zxc' size='340' side='right' caption='[[2zxc]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='2zxc' size='340' side='right'caption='[[2zxc]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zxc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZXC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zxc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZXC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2ED:N-[(1R,2R,3E)-2-HYDROXY-1-(HYDROXYMETHYL)HEPTADEC-3-EN-1-YL]ACETAMIDE'>2ED</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.2Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ceramidase Ceramidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.23 3.5.1.23] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ED:N-[(1R,2R,3E)-2-HYDROXY-1-(HYDROXYMETHYL)HEPTADEC-3-EN-1-YL]ACETAMIDE'>2ED</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2zxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zxc OCA], [http://pdbe.org/2zxc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zxc RCSB], [http://www.ebi.ac.uk/pdbsum/2zxc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zxc 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=2zxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zxc OCA], [https://pdbe.org/2zxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zxc RCSB], [https://www.ebi.ac.uk/pdbsum/2zxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zxc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCASE_PSEAE NCASE_PSEAE]] Catalyzes the cleavage of the N-acyl linkage of the ceramides (Cers) to yield sphingosine (Sph) and free fatty acid at an optimal pH of 8-9. Also catalyzes the synthesis of Cers from Sph and fatty acid.<ref>PMID:9603946</ref> <ref>PMID:19088069</ref> | + | [https://www.uniprot.org/uniprot/NCASE_PSEAE NCASE_PSEAE] Catalyzes the cleavage of the N-acyl linkage of the ceramides (Cers) to yield sphingosine (Sph) and free fatty acid at an optimal pH of 8-9. Also catalyzes the synthesis of Cers from Sph and fatty acid.<ref>PMID:9603946</ref> <ref>PMID:19088069</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/2zxc_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/2zxc_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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| | </div> | | </div> |
| | <div class="pdbe-citations 2zxc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2zxc" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ceramidase|Ceramidase]] |
| | + | *[[Ceramidase 3D PDB structures|Ceramidase 3D PDB structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ceramidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Inoue, T]] | + | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: Ito, M]] | + | [[Category: Inoue T]] |
| - | [[Category: Kakuta, Y]] | + | [[Category: Ito M]] |
| - | [[Category: Matsumura, H]] | + | [[Category: Kakuta Y]] |
| - | [[Category: Okano, H]] | + | [[Category: Matsumura H]] |
| - | [[Category: Okino, N]] | + | [[Category: Okano H]] |
| - | [[Category: Beta-prism fold surrounded by six alpha helix]]
| + | [[Category: Okino N]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipid metabolism]]
| + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
2zxc is a 2 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.2Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
NCASE_PSEAE Catalyzes the cleavage of the N-acyl linkage of the ceramides (Cers) to yield sphingosine (Sph) and free fatty acid at an optimal pH of 8-9. Also catalyzes the synthesis of Cers from Sph and fatty acid.[1] [2]
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
Ceramidase (CDase; EC 3.5.1.23) hydrolyzes ceramide to generate sphingosine and fatty acid. The enzyme plays a regulatory role in a variety of physiological events in eukaryotes and also functions as an exotoxin in particular bacteria. The crystal structures of neutral CDase from Pseudomonas aeruginosa (PaCD) in the C2-ceramide-bound and -unbound forms were determined at 2.2 and 1.4 A resolutions, respectively. PaCD consists of two domains, and the Zn(2+)- and Mg(2+)/Ca(2+)-binding sites are found within the center of the N-terminal domain and the interface between the domains, respectively. The structural comparison between the C2-ceramide-bound and unbound forms revealed an open-closed conformational change occurring to loop I upon binding of C2-ceramide. In the closed state, this loop sits above the Zn(2+) coordination site and over the opening to the substrate binding site. Mutational analyses of residues surrounding the Zn(2+) of PaCD and rat neutral CDase revealed that the cleavage or creation of the N-acyl linkage of ceramide follows a similar mechanism as observed for the Zn(2+)-dependent carboxypeptidases. The results provide an understanding of the molecular mechanism of hydrolysis and synthesis of ceramide by the enzyme. Furthermore, insights into the actions of PaCD and eukaryotic neutral CDases as an exotoxin and mediators of sphingolipid signaling are also revealed, respectively.
Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral ceramidase.,Inoue T, Okino N, Kakuta Y, Hijikata A, Okano H, Goda HM, Tani M, Sueyoshi N, Kambayashi K, Matsumura H, Kai Y, Ito M J Biol Chem. 2009 Apr 3;284(14):9566-77. Epub 2008 Dec 16. PMID:19088069[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Okino N, Tani M, Imayama S, Ito M. Purification and characterization of a novel ceramidase from Pseudomonas aeruginosa. J Biol Chem. 1998 Jun 5;273(23):14368-73. PMID:9603946
- ↑ Inoue T, Okino N, Kakuta Y, Hijikata A, Okano H, Goda HM, Tani M, Sueyoshi N, Kambayashi K, Matsumura H, Kai Y, Ito M. Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral ceramidase. J Biol Chem. 2009 Apr 3;284(14):9566-77. Epub 2008 Dec 16. PMID:19088069 doi:10.1074/jbc.M808232200
- ↑ Inoue T, Okino N, Kakuta Y, Hijikata A, Okano H, Goda HM, Tani M, Sueyoshi N, Kambayashi K, Matsumura H, Kai Y, Ito M. Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral ceramidase. J Biol Chem. 2009 Apr 3;284(14):9566-77. Epub 2008 Dec 16. PMID:19088069 doi:10.1074/jbc.M808232200
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