4u98

Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway (AppCp complex)

spinqualitylabelsall models 4u98, resolution 1.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4u98 is a 1 chain structure with sequence from Mycolicibacterium vanbaalenii PYR-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.15Å Ligands: ACP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MAK_MYCVP Catalyzes the ATP-dependent phosphorylation of maltose to maltose 1-phosphate. Is involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, GlgE and GlgB (By similarity). Publication Abstract from PubMed A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 A structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds. Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway.,Fraga J, Maranha A, Mendes V, Pereira PJ, Empadinhas N, Macedo-Ribeiro S Sci Rep. 2015 Jan 26;5:8026. doi: 10.1038/srep08026. PMID:25619172 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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