4m5h

The Identification, Analysis and Structure-Based Development of Novel Inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase

spinqualitylabelsall models 4m5h, resolution 1.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4m5h is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.11Å Ligands: APC, CA, CL, YH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HPPK_ECOLI Publication Abstract from PubMed 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is an essential enzyme in the microbial folate biosynthetic pathway. This pathway has proven to be an excellent target for antimicrobial development, but widespread resistance to common therapeutics including the sulfa drugs has stimulated interest in HPPK as an alternative target in the pathway. A screen of a pterin-biased compound set identified several HPPK inhibitors that contain an aryl substituted 8-thioguanine scaffold, and structural analyses showed that these compounds engage the HPPK pterin-binding pocket and an induced cryptic pocket. A preliminary structure activity relationship profile was developed from biophysical and biochemical characterizations of derivative molecules. Also, a similarity search identified additional scaffolds that bind more tightly within the HPPK pterin pocket. These inhibitory scaffolds have the potential for rapid elaboration into novel lead antimicrobial agents. The identification, analysis and structure-based development of novel inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase.,Yun MK, Hoagland D, Kumar G, Waddell MB, Rock CO, Lee RE, White SW Bioorg Med Chem. 2014 Apr 1;22(7):2157-65. doi: 10.1016/j.bmc.2014.02.022. Epub, 2014 Feb 25. PMID:24613625 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also HPPK 3D structures

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