5yg3: Difference between revisions

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-'''Unreleased structure'''
-The entry 5yg3 is ON HOLD  until Paper Publication
+==Plasmodium vivax SHMT bound with PLP-glycine and S-GS834==
+<StructureSection load='5yg3' size='340' side='right' caption='[[5yg3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5yg3]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YG3 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8UC:(3~{S})-6-azanyl-7-fluoranyl-2,2,3-trimethyl-5-pyridin-4-yl-spiro[1~{H}-indene-3,4-2~{H}-pyrano[2,3-c]pyrazole]-5-carbonitrile'>8UC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PLG:N-GLYCINE-[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YL-METHANE]'>PLG</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycine_hydroxymethyltransferase Glycine hydroxymethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.1 2.1.2.1] </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=5yg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yg3 OCA], [http://pdbe.org/5yg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yg3 RCSB], [http://www.ebi.ac.uk/pdbsum/5yg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yg3 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+With the discovery that serine hydroxymethyltransferase (SHMT) is a druggable target for antimalarials, the aim of this study was to design novel inhibitors of this key enzyme in the folate biosynthesis cycle. Herein, 19 novel spirocyclic ligands based on either 2-indolinone or dihydroindene scaffolds and featuring a pyrazolopyran core are reported. Strong target affinities for Plasmodium falciparum (Pf) SHMT (14-76 nm) and cellular potencies in the low nanomolar range (165-334 nm) were measured together with interesting selectivity against human cytosolic SHMT1 (hSHMT1). Four co-crystal structures with Plasmodium vivax (Pv) SHMT solved at 2.2-2.4 A resolution revealed the key role of the vinylogous cyanamide for anchoring ligands within the active site. The spirocyclic motif in the molecules enforces the pyrazolopyran core to adopt a substantially more curved conformation than that of previous non-spirocyclic analogues. Finally, solvation of the spirocyclic lactam ring of the receptor-bound ligands is discussed.
-Authors: Chitnumsub, P., Jaruwat, A., Leartsakulpanich, U., Schwertz, G., Diederich, F.
+Potent Inhibitors of Plasmodial Serine Hydroxymethyltransferase (SHMT) Featuring a Spirocyclic Scaffold.,Schwertz G, Witschel MC, Rottmann M, Leartsakulpanich U, Chitnumsub P, Jaruwat A, Amornwatcharapong W, Ittarat W, Schafer A, Aponte RA, Trapp N, Chaiyen P, Diederich F ChemMedChem. 2018 May 8;13(9):931-943. doi: 10.1002/cmdc.201800053. Epub 2018 Apr, 14. PMID:29655285<ref>PMID:29655285</ref>
-Description: Plasmodium vivax SHMT bound with PLP-glycine and S-GS834
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Jaruwat, A]]
+<div class="pdbe-citations 5yg3" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Glycine hydroxymethyltransferase]]
 [[Category: Chitnumsub, P]]
 [[Category: Diederich, F]]
+[[Category: Jaruwat, A]]
+[[Category: Leartsakulpanich, U]]
 [[Category: Schwertz, G]]
-[[Category: Leartsakulpanich, U]]
+[[Category: Alpha and beta protein]]
+[[Category: Inhibitor]]
+[[Category: Methyltransferase activity]]
+[[Category: Transferase]]
+[[Category: Transferase-inhibitor complex]]