4al1: Difference between revisions
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==Crystal structure of Human PS-1 GSH-analog complex== | |||
<StructureSection load='4al1' size='340' side='right' caption='[[4al1]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4al1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AL1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AL1 FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=48T:L-GAMMA-GLUTAMYL-S-(2-BIPHENYL-4-YL-2-OXOETHYL)-L-CYSTEINYLGLYCINE'>48T</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4al0|4al0]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></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=4al1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4al1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4al1 RCSB], [http://www.ebi.ac.uk/pdbsum/4al1 PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/PTGES_HUMAN PTGES_HUMAN]] Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).<ref>PMID:18682561</ref> | [[http://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> | ||
<references | </div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Prostaglandin-E synthase]] | [[Category: Prostaglandin-E synthase]] | ||
[[Category: Ek, M | [[Category: Ek, M]] | ||
[[Category: Geschwindner, S | [[Category: Geschwindner, S]] | ||
[[Category: Johansson, P | [[Category: Johansson, P]] | ||
[[Category: Liu, G | [[Category: Liu, G]] | ||
[[Category: Nord, J | [[Category: Nord, J]] | ||
[[Category: Sjogren, T | [[Category: Sjogren, T]] | ||
[[Category: Isomerase]] | [[Category: Isomerase]] | ||
[[Category: Lipid biosynthesis]] | [[Category: Lipid biosynthesis]] | ||
[[Category: Membrane protein]] | [[Category: Membrane protein]] | ||
Revision as of 18:56, 25 December 2014
Crystal structure of Human PS-1 GSH-analog complexCrystal structure of Human PS-1 GSH-analog complex
Structural highlights
Function[PTGES_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. References
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