4cn4 | pdb_00004cn4

GlgE isoform 1 from Streptomyces coelicolor E423A mutant with 2-deoxy- 2-fluoro-beta-maltosyl modification

spinqualitylabelsall models 4cn4, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cn4 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GLC, SHG Related: 4cn1, 4cn6 Activity: Starch synthase (maltosyl-transferring), with EC number 2.4.99.16 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed GlgE (EC 2.4.99.16) is an alpha-maltose 1-phosphate:(1-->4)-alpha-d-glucan 4-alpha-d-maltosyltransferase of the CAZy glycoside hydrolase 13_3 family. It is the defining enzyme of a bacterial alpha-glucan biosynthetic pathway and is a genetically validated anti-tuberculosis target. It catalyzes the alpha-retaining transfer of maltosyl units from alpha-maltose 1-phosphate to maltooligosaccharides and is predicted to use a double-displacement mechanism. Evidence of this mechanism was obtained using a combination of site-directed mutagenesis of Streptomyces coelicolor GlgE isoform I, substrate analogues, protein crystallography, and mass spectrometry. The X-ray structures of alpha-maltose 1-phosphate bound to a D394A mutein and a beta-2-deoxy-2-fluoromaltosyl-enzyme intermediate with a E423A mutein were determined. There are few examples of CAZy glycoside hydrolase family 13 members that have had their glycosyl-enzyme intermediate structures determined, and none before now have been obtained with a 2-deoxy-2-fluoro substrate analogue. The covalent modification of Asp394 was confirmed using mass spectrometry. A similar modification of wild-type GlgE proteins from S. coelicolor and Mycobacterium tuberculosis was also observed. Small-angle X-ray scattering of the M. tuberculosis enzyme revealed a homodimeric assembly similar to that of the S. coelicolor enzyme but with slightly differently oriented monomers. The deeper understanding of the structure-function relationships of S. coelicolor GlgE will aid the development of inhibitors of the M. tuberculosis enzyme. Structural Insight into How Streptomyces coelicolor Maltosyl Transferase GlgE Binds alpha-Maltose 1-Phosphate and Forms a Maltosyl-enzyme Intermediate.,Syson K, Stevenson CE, Rashid AM, Saalbach G, Tang M, Tuukkanen A, Svergun DI, Withers SG, Lawson DM, Bornemann S Biochemistry. 2014 Apr 22;53(15):2494-504. doi: 10.1021/bi500183c. Epub 2014 Apr , 11. PMID:24689960 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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