5xmq | pdb_00005xmq

Plasmodium vivax SHMT(C346A) bound with PLP-glycine and MF011

spinqualitylabelsall models 5xmq, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xmq is a 3 chain structure with sequence from Plasmodium vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: 8A6, CL, PLG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A5K8L9_PLAVS 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine hydroxymethyltransferase 3D structures

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