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| - | [[Image:2pbj.jpg|left|200px]]<br /><applet load="2pbj" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2pbj, resolution 2.8Å" /> | |
| - | '''GSH-heme bound microsomal prostaglandin E synthase'''<br /> | |
| | | | |
| - | ==Overview== | + | ==GSH-heme bound microsomal prostaglandin E synthase== |
| - | 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.
| + | <StructureSection load='2pbj' size='340' side='right'caption='[[2pbj]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | + | == Structural highlights == |
| | + | <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='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='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='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> |
| | + | == 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. |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pb/2pbj_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </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> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | 2PBJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Macaca_fascicularis Macaca fascicularis] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=GSH:'>GSH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Prostaglandin-E_synthase Prostaglandin-E synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.99.3 5.3.99.3] Known structural/functional Sites: <scene name='pdbsite=AC1:Cl+Binding+Site+For+Residue+A+475'>AC1</scene>, <scene name='pdbsite=AC2:Cl+Binding+Site+For+Residue+B+475'>AC2</scene>, <scene name='pdbsite=AC3:Cl+Binding+Site+For+Residue+C+475'>AC3</scene>, <scene name='pdbsite=AC4:Cl+Binding+Site+For+Residue+D+475'>AC4</scene>, <scene name='pdbsite=AC5:Hem+Binding+Site+For+Residue+A+476'>AC5</scene>, <scene name='pdbsite=AC6:Gsh+Binding+Site+For+Residue+A+477'>AC6</scene>, <scene name='pdbsite=AC7:Hem+Binding+Site+For+Residue+B+476'>AC7</scene>, <scene name='pdbsite=AC8:Gsh+Binding+Site+For+Residue+B+477'>AC8</scene>, <scene name='pdbsite=AC9:Hem+Binding+Site+For+Residue+C+476'>AC9</scene>, <scene name='pdbsite=BC1:Gsh+Binding+Site+For+Residue+C+477'>BC1</scene>, <scene name='pdbsite=BC2:Hem+Binding+Site+For+Residue+D+476'>BC2</scene> and <scene name='pdbsite=BC3:Gsh+Binding+Site+For+Residue+D+477'>BC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PBJ OCA].
| + | *[[Prostaglandin E synthase|Prostaglandin E synthase]] |
| - | | + | __TOC__ |
| - | ==Reference==
| + | </StructureSection> |
| - | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17585783 17585783]
| + | [[Category: Large Structures]] |
| | [[Category: Macaca fascicularis]] | | [[Category: Macaca fascicularis]] |
| - | [[Category: Prostaglandin-E synthase]]
| + | [[Category: Takusagawa F]] |
| - | [[Category: Single protein]]
| + | [[Category: Yamada T]] |
| - | [[Category: Takusagawa, F.]] | + | |
| - | [[Category: Yamada, T.]] | + | |
| - | [[Category: CL]]
| + | |
| - | [[Category: GSH]]
| + | |
| - | [[Category: HEM]]
| + | |
| - | [[Category: dual function enzyme]]
| + | |
| - | [[Category: gsh-heme bound enzyme]]
| + | |
| - | [[Category: isomerase]]
| + | |
| - | [[Category: lyase]]
| + | |
| - | [[Category: prostaglandin e synthase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:20:10 2008''
| + | |
