7mpk

Crystal structure of TagA with UDP-GlcNAc

spinqualitylabelsall models 7mpk, resolution 2.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7mpk is a 3 chain structure with sequence from Thermoanaerobacter italicus Ab9. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.993Å Ligands: UD1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D3T4E0_THEIA Catalyzes the conversion of GlcNAc-PP-undecaprenol into ManNAc-GlcNAc-PP-undecaprenol, the first committed lipid intermediate in the de novo synthesis of teichoic acid.[HAMAP-Rule:MF_02070] Publication Abstract from PubMed Wall teichoic acid (WTA) polymers are covalently affixed to the Gram-positive bacterial cell wall and have important functions in cell elongation, cell morphology, biofilm formation, and beta-lactam antibiotic resistance. The first committed step in WTA biosynthesis is catalyzed by the TagA glycosyltransferase (also called TarA), a peripheral membrane protein that produces the conserved linkage unit which joins WTA to the cell wall peptidoglycan. TagA contains a conserved GT26 core domain followed by a C-terminal polypeptide tail (CTT) that is important for catalysis and membrane binding. Here we report the crystal structure of the Thermoanaerobacter italicus TagA enzyme bound to UDP-ManNAc, revealing the molecular basis of substrate binding. Native mass spectrometry experiments support the model that only monomeric TagA is enzymatically active and that it is stabilized by membrane binding. Molecular dynamics simulations and enzyme activity measurements indicate that the CTT facilitates catalysis by encapsulating the UDP-ManNAc substrate, presenting three highly conserved arginine residues to the active site that are important for catalysis (R214, R221, and R224). From these data we present a mechanistic model of catalysis that ascribes functions for these residues. This work could facilitate the development of new antimicrobial compounds that disrupt WTA biosynthesis in pathogenic bacteria. Insight into the molecular basis of substrate recognition by the wall teichoic acid glycosyltransferase TagA.,Martinez OE, Mahoney BJ, Goring AK, Yi SW, Tran DP, Cascio D, Phillips ML, Muthana MM, Chen X, Jung ME, Loo JA, Clubb RT J Biol Chem. 2021 Dec 2:101464. doi: 10.1016/j.jbc.2021.101464. PMID:34864059 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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