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| <StructureSection load='2pbj' size='340' side='right'caption='[[2pbj]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='2pbj' size='340' side='right'caption='[[2pbj]], [[Resolution|resolution]] 2.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[2pbj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Crab-eating_macaque Crab-eating macaque]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PBJ FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2pbj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_fascicularis Macaca fascicularis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PBJ FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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]] 2.8Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mPGES-2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9541 Crab-eating macaque])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Prostaglandin-E_synthase Prostaglandin-E synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.99.3 5.3.99.3] </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=2pbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pbj OCA], [https://pdbe.org/2pbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pbj RCSB], [https://www.ebi.ac.uk/pdbsum/2pbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pbj 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=2pbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pbj OCA], [https://pdbe.org/2pbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pbj RCSB], [https://www.ebi.ac.uk/pdbsum/2pbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pbj ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[https://www.uniprot.org/uniprot/PGES2_MACFA PGES2_MACFA]] Isomerase that catalyzes the conversion of unstable intermediate of prostaglandin E2 H2 (PGH2) into the more stable prostaglandin E2 (PGE2) form. May also have transactivation activity toward IFN-gamma (IFNG), possibly via an interaction with CEBPB; however, the relevance of transcription activation activity remains unclear.
| | [https://www.uniprot.org/uniprot/PGES2_MACFA PGES2_MACFA] Isomerase that catalyzes the conversion of unstable intermediate of prostaglandin E2 H2 (PGH2) into the more stable prostaglandin E2 (PGE2) form. May also have transactivation activity toward IFN-gamma (IFNG), possibly via an interaction with CEBPB; however, the relevance of transcription activation activity remains unclear. |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pbj ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pbj ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Prostaglandin E2 synthase (PGES) catalyzes the isomerization of PGH2 to PGE2. PGES type 2 (mPGES-2) is a membrane-associated enzyme, whose N-terminal section is apparently inserted into the lipid bilayer. Both intact and N-terminal truncated enzymes have been isolated and have similar catalytic activity. The recombinant N-terminal truncated enzyme purified from Escherichia coli HB101 grown in LB medium containing delta-aminolevulinate and Fe(NO3)3 has a red color, while the same enzyme purified from the same E. coli grown in minimal medium has no color. The red-colored enzyme has been characterized by mass, fluorescence, and EPR spectroscopies and X-ray crystallography. The enzyme is found to contain bound glutathione (GSH) and heme. GSH binds to the active site with six H-bonds, while a heme is complexed with bound GSH forming a S-Fe coordination bond with no polar interaction with mPGES-2. There is a large open space between the heme and the protein, where a PGH2 might be able to bind. The heme dissociation constant is 0.53 microM, indicating that mPGES-2 has relatively strong heme affinity. Indeed, expression of mPGES-2 in E. coli stimulates heme biosynthesis. Although mPGES-2 has been reported to be a GSH-independent PGES, the crystal structure and sequence analysis indicate that mPGES-2 is a GSH-binding protein. The GSH-heme complex-bound enzyme (mPGES-2h) catalyzes formation of 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid and malondialdehyde from PGH2, but not formation of PGE2. The following kinetic parameters at 37 degrees C were determined: KM = 56 microM, kcat = 63 s-1, and kcat/KM = 1.1 x 10(6) M-1 s-1. They suggest that mPGES-2h has significant catalytic activity for PGH2 degradation. It is possible that both GSH-heme complex-free and -bound enzymes are present in the same tissues. mPGES-2 in heme-rich liver is most likely to become the form of mPGES-2h and might be involved in degradation reactions similar to that of cytochrome P450. Since mPGES-2 is an isomerase and mPGES-2h is a lyase, mPGES-2 cannot simply be classified into one of six classes set by the International Union of Biochemistry and Molecular Biology.
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| PGH2 degradation pathway catalyzed by GSH-heme complex bound microsomal prostaglandin E2 synthase type 2: the first example of a dual-function enzyme.,Yamada T, Takusagawa F Biochemistry. 2007 Jul 17;46(28):8414-24. Epub 2007 Jun 22. PMID:17585783<ref>PMID:17585783</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 2pbj" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Prostaglandin E synthase|Prostaglandin E synthase]] | | *[[Prostaglandin E synthase|Prostaglandin E synthase]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Crab-eating macaque]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Prostaglandin-E synthase]] | | [[Category: Macaca fascicularis]] |
| [[Category: Takusagawa, F]] | | [[Category: Takusagawa F]] |
| [[Category: Yamada, T]] | | [[Category: Yamada T]] |
| [[Category: Dual function enzyme]]
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| [[Category: Gsh-heme bound enzyme]]
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| [[Category: Isomerase]]
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| [[Category: Lyase]]
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| [[Category: Prostaglandin e synthase]]
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