4lis

Crystal Structure of UDP-galactose-4-epimerase from Aspergillus nidulans

spinqualitylabelsall models 4lis, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lis is a 3 chain structure with sequence from Aspergillus nidulans FGSC A4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: GOL, IOD, NAD, UDP, UPG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C8VAU8_EMENI Publication Abstract from PubMed The frequency of invasive fungal infections has rapidly increased in recent years. Current clinical treatments are experiencing decreased potency due to severe host toxicity and the emergence of fungal drug resistance. As such, new targets and their corresponding synthetic pathways need to be explored for drug development purposes. In this context, galactofuranose residues, which are employed in fungal cell wall construction, but are notably absent in animals, represent an appealing target. Herein we present the structural and biochemical characterization of UDP-galactose-4-epimerase from Aspergillus nidulans which produces the precursor UDP-galactopyranose required for galactofuranose synthesis. Examination of the structural model revealed both NAD(+) and UDP-glucopyranose were bound within the active site cleft in a near identical fashion to that found in the Human epimerase. Mutational studies on the conserved catalytic motif support a similar mechanism to that established for the Human counterpart is likely operational within the A. nidulans epimerase. While the K m and k cat for the enzyme were determined to be 0.11 mM and 12.8 s(-1), respectively, a single point mutation, namely L320C, activated the enzyme towards larger N-acetylated substrates. Docking studies designed to probe active site affinity corroborate the experimentally determined activity profiles and support the kinetic inhibition results. Elucidation of Substrate Specificity in Aspergillus nidulans UDP-Galactose-4-Epimerase.,Dalrymple SA, Ko J, Sheoran I, Kaminskyj SG, Sanders DA PLoS One. 2013 Oct 7;8(10):e76803. doi: 10.1371/journal.pone.0076803. PMID:24116166 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also UDP-galactose 4-epimerase

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