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[[Image:1z9h.gif|left|200px]]<br /><applet load="1z9h" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1z9h, resolution 2.6&Aring;" />
'''Microsomal prostaglandin E synthase type-2'''<br />


==Overview==
==Microsomal prostaglandin E synthase type-2==
Prostaglandin (PG) H(2) (PGH(2)), formed from arachidonic acid, is an unstable intermediate and is converted efficiently into more stable arachidonate metabolites (PGD(2), PGE(2), and PGF(2)) by the action of three groups of enzymes. Prostaglandin E synthase catalyzes an isomerization reaction, PGH(2) to PGE(2). Microsomal prostaglandin E synthase type-2 (mPGES-2) has been crystallized with an anti-inflammatory drug indomethacin (IMN), and the complex structure has been determined at 2.6A resolution. mPGES-2 forms a dimer and is attached to lipid membrane by anchoring the N-terminal section. Two hydrophobic pockets connected to form a V shape are located in the bottom of a large cavity. IMN binds deeply in the cavity by placing the OMe-indole and chlorophenyl moieties into the V-shaped pockets, respectively, and the carboxyl group interacts with S(gamma) of C110 by forming a H-bond. A characteristic H-bond chain formation (N-H...S(gamma)-H...S(gamma)...H-N) is seen through Y107-C113-C110-F112, which apparently decreases the pK(a) of S(gamma) of C110. The geometry suggests that the S(gamma) of C110 is most likely the catalytic site of mPGES-2. A search of the RCSB Protein Data Bank suggests that IMN can fit into the PGH(2) binding site in various proteins. On the basis of the crystal structure and mutation data, a PGH(2)-bound model structure was built. PGH(2) fits well into the IMN binding site by placing the alpha and omega-chains in the V-shaped pockets, and the endoperoxide moiety interacts with S(gamma) of C110. A possible catalytic mechanism is proposed on the basis of the crystal and model structures, and an alternative catalytic mechanism is described. The fold of mPGES-2 is quite similar to those of GSH-dependent hematopoietic prostaglandin D synthase, except for the two large loop sections.
<StructureSection load='1z9h' size='340' side='right'caption='[[1z9h]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1z9h]] 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=1Z9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z9H 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IMN:INDOMETHACIN'>IMN</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=1z9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z9h OCA], [https://pdbe.org/1z9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z9h RCSB], [https://www.ebi.ac.uk/pdbsum/1z9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z9h 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/z9/1z9h_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=1z9h ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1Z9H 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=ACT:'>ACT</scene> and <scene name='pdbligand=IMN:'>IMN</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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z9H OCA].
*[[Prostaglandin E synthase|Prostaglandin E synthase]]
 
__TOC__
==Reference==
</StructureSection>
Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2)., Yamada T, Komoto J, Watanabe K, Ohmiya Y, Takusagawa F, J Mol Biol. 2005 May 20;348(5):1163-76. Epub 2005 Apr 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15854652 15854652]
[[Category: Large Structures]]
[[Category: Macaca fascicularis]]
[[Category: Macaca fascicularis]]
[[Category: Prostaglandin-E synthase]]
[[Category: Komoto J]]
[[Category: Single protein]]
[[Category: Ohmiya Y]]
[[Category: Komoto, J.]]
[[Category: Takusagawa F]]
[[Category: Ohmiya, Y.]]
[[Category: Watanabe K]]
[[Category: Takusagawa, F.]]
[[Category: Yamada T]]
[[Category: Watanabe, K.]]
[[Category: Yamada, T.]]
[[Category: ACT]]
[[Category: CL]]
[[Category: IMN]]
[[Category: indomethacin]]
[[Category: membran associated protein]]
[[Category: prostaglandin e synthase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:13:24 2008''

Latest revision as of 12:02, 14 February 2024

Microsomal prostaglandin E synthase type-2Microsomal prostaglandin E synthase type-2

Structural highlights

1z9h is a 4 chain structure with sequence from Macaca fascicularis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1z9h, resolution 2.60Å

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