View source for 5xmr


==Plasmodium vivax SHMT(C346A) bound with PLP-glycine and GS395==
<StructureSection load='5xmr' size='340' side='right'caption='[[5xmr]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xmr]] 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=5XMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XMR 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]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8AO:(4~{S})-6-azanyl-3-methyl-4-[3-[4-(phenylmethyl)sulfonylphenyl]-5-(trifluoromethyl)phenyl]-4-propan-2-yl-2~{H}-pyrano[2+,3-c]pyrazole-5-carbonitrile'>8AO</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5xmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xmr OCA], [https://pdbe.org/5xmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xmr RCSB], [https://www.ebi.ac.uk/pdbsum/5xmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xmr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A5K8L9_PLAVS A5K8L9_PLAVS] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Malaria remains a major threat to mankind due to the perpetual emergence of resistance against marketed drugs. Twenty-one pyrazolopyran-based inhibitors bearing terminal biphenyl, aryl sulfonamide, or aryl sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), a key enzyme of the folate cycle. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target, as well as PfNF54 strains in cell-based assays in the low nanomolar range (18-56 nm). Seven co-crystal structures with P. vivax (Pv) SHMT were solved at 2.2-2.6 A resolution. We observed an unprecedented influence of the torsion angle of ortho-substituted biphenyl moieties on cell-based efficacy. The peculiar lipophilic character of the sulfonyl moiety was highlighted in the complexes with aryl sulfonamide analogues, which bind in their preferred staggered orientation. The results are discussed within the context of conformational preferences in the ligands.

Conformational Aspects in the Design of Inhibitors for Serine Hydroxymethyltransferase (SHMT): Biphenyl, Aryl Sulfonamide, and Aryl Sulfone Motifs.,Schwertz G, Frei MS, Witschel MC, Rottmann M, Leartsakulpanich U, Chitnumsub P, Jaruwat A, Ittarat W, Schafer A, Aponte RA, Trapp N, Mark K, Chaiyen P, Diederich F Chemistry. 2017 Oct 12;23(57):14345-14357. doi: 10.1002/chem.201703244. Epub 2017, Oct 2. PMID:28967982<ref>PMID:28967982</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xmr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine hydroxymethyltransferase 3D structures|Serine hydroxymethyltransferase 3D structures]]
== 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]]