5yg2: Difference between revisions

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-'''Unreleased structure'''
-The entry 5yg2 is ON HOLD
+==Plasmodium vivax SHMT bound with PLP-glycine and GS705==
+<StructureSection load='5yg2' size='340' side='right'caption='[[5yg2]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5yg2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YG2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YG2 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=N05:3-[1-[3-[(4~{S})-6-azanyl-5-cyano-3-methyl-4-propan-2-yl-2~{H}-pyrano[2,3-c]pyrazol-4-yl]-5-fluoranyl-phenyl]piperidin-4-yl]propanoic+acid'>N05</scene>, <scene name='pdbligand=PLG:N-GLYCINE-[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YL-METHANE]'>PLG</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=5yg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yg2 OCA], [https://pdbe.org/5yg2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yg2 RCSB], [https://www.ebi.ac.uk/pdbsum/5yg2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yg2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A1G4H5I1_PLAVI A0A1G4H5I1_PLAVI]
+<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 GS705
+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 5yg2" style="background-color:#fffaf0;"></div>
-[[Category: Leartsakulpanich, U]]
-[[Category: Schwertz, G]]
+==See Also==
-[[Category: Chitnumsub, P]]
+*[[Serine hydroxymethyltransferase 3D structures|Serine hydroxymethyltransferase 3D structures]]
-[[Category: Diederich, F]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Plasmodium vivax]]
+[[Category: Chitnumsub P]]
+[[Category: Diederich F]]
+[[Category: Jaruwat A]]
+[[Category: Leartsakulpanich U]]
+[[Category: Schwertz G]]