4al0: Difference between revisions
New page: '''Unreleased structure''' The entry 4al0 is ON HOLD Authors: Sjogren, T., Nord, J., Ek, M., Johansson, P., Liu, G., Geschwindner, S. Description: Crystal structure of Human PS-1 |
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The | ==Crystal structure of Human PS-1== | ||
<StructureSection load='4al0' size='340' side='right'caption='[[4al0]], [[Resolution|resolution]] 1.16Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4al0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AL0 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]] 1.16Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=4al0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4al0 OCA], [https://pdbe.org/4al0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4al0 RCSB], [https://www.ebi.ac.uk/pdbsum/4al0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4al0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PTGES_HUMAN PTGES_HUMAN] Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).<ref>PMID:18682561</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Prostaglandin E (PGE) is a key mediator in inflammatory response. The main source of inducible PGE, microsomal PGE synthase-1 (mPGES-1), has emerged as an interesting drug target for treatment of pain. To support inhibitor design, we have determined the crystal structure of human mPGES-1 to 1.2 A resolution. The structure reveals three well-defined active site cavities within the membrane-spanning region in each monomer interface of the trimeric structure. An important determinant of the active site cavity is a small cytosolic domain inserted between transmembrane helices I and II. This extra domain is not observed in other structures of proteins within the MAPEG (Membrane-Associated Proteins involved in Eicosanoid and Glutathione metabolism) superfamily but is likely to be present also in microsomal GST-1 based on sequence similarity. An unexpected feature of the structure is a 16-A-deep cone-shaped cavity extending from the cytosolic side into the membrane-spanning region. We suggest a potential role for this cavity in substrate access. Based on the structure of the active site, we propose a catalytic mechanism in which serine 127 plays a key role. We have also determined the structure of mPGES-1 in complex with a glutathione-based analog, providing insight into mPGES-1 flexibility and potential for structure-based drug design. | |||
Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily.,Sjogren T, Nord J, Ek M, Johansson P, Liu G, Geschwindner S Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3806-11. doi:, 10.1073/pnas.1218504110. Epub 2013 Feb 19. PMID:23431194<ref>PMID:23431194</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4al0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Prostaglandin E synthase|Prostaglandin E synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ek M]] | |||
[[Category: Geschwindner S]] | |||
[[Category: Johansson P]] | |||
[[Category: Liu G]] | |||
[[Category: Nord J]] | |||
[[Category: Sjogren T]] | |||
Latest revision as of 13:51, 9 May 2024
Crystal structure of Human PS-1Crystal structure of Human PS-1
Structural highlights
FunctionPTGES_HUMAN Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).[1] Publication Abstract from PubMedProstaglandin E (PGE) is a key mediator in inflammatory response. The main source of inducible PGE, microsomal PGE synthase-1 (mPGES-1), has emerged as an interesting drug target for treatment of pain. To support inhibitor design, we have determined the crystal structure of human mPGES-1 to 1.2 A resolution. The structure reveals three well-defined active site cavities within the membrane-spanning region in each monomer interface of the trimeric structure. An important determinant of the active site cavity is a small cytosolic domain inserted between transmembrane helices I and II. This extra domain is not observed in other structures of proteins within the MAPEG (Membrane-Associated Proteins involved in Eicosanoid and Glutathione metabolism) superfamily but is likely to be present also in microsomal GST-1 based on sequence similarity. An unexpected feature of the structure is a 16-A-deep cone-shaped cavity extending from the cytosolic side into the membrane-spanning region. We suggest a potential role for this cavity in substrate access. Based on the structure of the active site, we propose a catalytic mechanism in which serine 127 plays a key role. We have also determined the structure of mPGES-1 in complex with a glutathione-based analog, providing insight into mPGES-1 flexibility and potential for structure-based drug design. Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily.,Sjogren T, Nord J, Ek M, Johansson P, Liu G, Geschwindner S Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3806-11. doi:, 10.1073/pnas.1218504110. Epub 2013 Feb 19. PMID:23431194[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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