4g5f

Pantothenate synthetase in complex with racemate (2S)-2,3-DIHYDRO-1,4-BENZODIOXINE-2-CARBOXYLIC ACID and (2R)-2,3-DIHYDRO-1,4-BENZODIOXINE-2-CARBOXYLIC ACID

spinqualitylabelsall models 4g5f, resolution 2.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g5f is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0JD, 15N, EDO, EOH, GOL Related: 4ddh, 4ddk, 4ddm, 4ef6, 4efk, 4fzj Gene: MT3707, MTCY07H7B.20, panC, Rv3602c (Mycobacterium tuberculosis) Activity: Pantoate--beta-alanine ligase, with EC number 6.3.2.1 Resources: FirstGlance, OCA, RCSB, PDBsum Function [PANC_MYCTU] Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate. Publication Abstract from PubMed In fragment-based drug discovery, the weak affinities exhibited by fragments pose significant challenges for screening. Biophysical techniques are used to address this challenge, but there is no clear consensus on which cascade of methods is best suited to identify fragment hits that ultimately translate into bound X-ray structures and provide bona fide starting points for synthesis. We have benchmarked an integrated biophysical approach for fragment screening and validation against Mycobacterium tuberculosis pantothenate synthetase. A primary screen of 1,250 fragments library was performed by thermal shift, followed by secondary screen using one-dimensional NMR spectroscopy (water ligand observed gradient spectroscopy and saturation transfer difference binding experiments) and ultimate hit validation by isothermal titration calorimetry and X-ray crystallography. Our multibiophysical approach identified three distinct binding sites for fragments and laid a solid foundation for successful structure-based elaboration into potent inhibitors. Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery.,Silvestre HL, Blundell TL, Abell C, Ciulli A Proc Natl Acad Sci U S A. 2013 Jul 19. PMID:23872845 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pantothenate synthetase

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