4cax

Crystal structure of Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a pyrazole sulphonamide ligand (DDD85646)

spinqualitylabelsall models 4cax, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cax is a 1 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: 646, MYA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NMT_ASPFU Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins. Publication Abstract from PubMed Treatment of filamentous fungal infections relies on a limited repertoire of antifungal agents. Compounds possessing novel modes of action are urgently required. N-myristoylation is a ubiquitous modification of eukaryotic proteins. The enzyme N-myristoyltransferase (NMT) has been considered a potential therapeutic target in protozoa and yeasts. Here, we show that the filamentous fungal pathogen Aspergillus fumigatus possesses an active NMT enzyme that is essential for survival. Surprisingly, partial repression of the gene revealed downstream effects of N-myristoylation on cell wall morphology. Screening a library of inhibitors led to the discovery of a pyrazole sulphonamide compound that inhibits the enzyme and is fungicidal under partially repressive nmt conditions. Together with a crystallographic complex showing the inhibitor binding in the peptide substrate pocket, we provide evidence of NMT being a potential drug target in A. fumigatus. N-myristoyltransferase is a cell wall target in Aspergillus fumigatus.,Fang W, Robinson DA, Raimi OG, Blair DE, Harrison JR, Lockhart DE, Torrie LS, Ruda GF, Wyatt PG, Gilbert IH, van Aalten DM ACS Chem Biol. 2015 Jun 19;10(6):1425-34. doi: 10.1021/cb5008647. Epub 2015 Feb, 27. PMID:25706802 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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