6vl4

<table><tr><td colspan='2'>[[6vl4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VL4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VL4 FirstGlance]. <br>

</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=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=QY1:(2R)-cyclopentyl{4-[(quinolin-2-yl)methoxy]phenyl}acetic+acid'>QY1</scene></td></tr>

<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTGES, MGST1L1, MPGES1, PGES, PIG12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://proteopedia.org/fgij/fg.htm?mol=6vl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vl4 OCA], [http://pdbe.org/6vl4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vl4 RCSB], [http://www.ebi.ac.uk/pdbsum/6vl4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vl4 ProSAT]</span></td></tr>

== 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>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

BACKGROUND: Due to the importance of both prostaglandins (PGs) and leukotrienes (LTs) as pro-inflammatory mediators, and the potential for eicosanoid shunting in the presence of pathway target inhibitors, we have investigated an approach to inhibiting the formation of both PGs and LTs as part of a multi-targeted drug discovery effort. METHODS: We generated ligand-protein X-ray crystal structures of known inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) and the 5-Lipoxygenase Activating Protein (FLAP), with their respective proteins, to understand the overlapping pharmacophores. We subsequently used molecular modeling and structure-based drug design (SBDD) to identify hybrid structures intended to inhibit both targets. RESULTS: This work enabled the preparation of compounds 4 and 5, which showed potent in vitro inhibition of both targets. SIGNIFICANCE: Our findings enhance the structural understanding of mPGES-1 and FLAP's unique ligand binding pockets and should accelerate the discovery of additional dual inhibitors for these two important integral membrane protein drug targets.

 

== References ==

[[Category: Human]]

[[Category: Antonysamy, S]]

[[Category: Aznavour, K]]

[[Category: Chandrasekhar, S]]

[[Category: Condon, B]]

[[Category: Gooding, K]]

[[Category: Harvey, A]]

[[Category: Hickey, M J]]

[[Category: Ho, J D]]

[[Category: Hughes, N E]]

[[Category: Kahl, S D]]

[[Category: Lee, M R]]

[[Category: Luz, J G]]

[[Category: Maletic, M]]

[[Category: Norman, B H]]

[[Category: Park, J S]]

[[Category: Rauch, C T]]

[[Category: Sloan, A V]]

[[Category: Yu, X P]]

[[Category: Zhang, A]]

[[Category: Mpges-1]]