5yfz

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 5yfz is ON HOLD until Paper Publication
+
==Plasmodium vivax SHMT bound with PLP-glycine and S-GS626==
 +
<StructureSection load='5yfz' size='340' side='right' caption='[[5yfz]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[5yfz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YFZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YFZ FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8UO:2-[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]ethanoic+acid'>8UO</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=5yfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yfz OCA], [http://pdbe.org/5yfz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yfz RCSB], [http://www.ebi.ac.uk/pdbsum/5yfz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yfz 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-GS626
+
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 5yfz" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Glycine hydroxymethyltransferase]]
[[Category: Chitnumsub, P]]
[[Category: Chitnumsub, P]]
[[Category: Diederich, F]]
[[Category: Diederich, F]]
-
[[Category: Schwertz, G]]
+
[[Category: Jaruwat, A]]
[[Category: Leartsakulpanich, U]]
[[Category: Leartsakulpanich, U]]
 +
[[Category: Schwertz, G]]
 +
[[Category: Alpha and beta protein]]
 +
[[Category: Inhibitor]]
 +
[[Category: Methyltransferase activity]]
 +
[[Category: Transferase]]
 +
[[Category: Transferase-inhibitor complex]]

Revision as of 05:52, 6 June 2018

Plasmodium vivax SHMT bound with PLP-glycine and S-GS626

5yfz, resolution 2.16Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools