5vt4
From Proteopedia
Sco GlgEI-V279S in complex with a pyrolidene-based methyl-phosphonate compound
Structural highlights
Function[GLGE1_STRCO] Maltosyltransferase that uses maltose 1-phosphate (M1P) as the sugar donor to elongate linear or branched alpha-(1->4)-glucans. Maltooligosaccharides with a degree of polymerization (DP) superior or equal to 4 are efficient acceptors, with DP6 being optimal in the GlgE-catalyzed polymerization with M1P. Is specific for the alpha-anomer of M1P as substrate, since the beta-anomer of M1P gives no activity. Alpha-D-glucose 1-phosphate cannot serve as a donor substrate, but alpha-maltosyl fluoride is an efficient donor in vitro. Exhibits an alpha-retaining catalytic mechanism, with evidence that maltooligosaccharide acceptors are extended at their non-reducing ends. Is also able to catalyze the reverse reaction in vitro, releasing M1P from glycogen or maltoheptaose in the presence of inorganic phosphate. Also catalyzes disproportionation reactions through maltosyl transfer between maltooligosaccharides. Is probably involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Mak and GlgB.[1] Publication Abstract from PubMedWe synthesized and evaluated new zwitterionic inhibitors against glycoside hydrolase-like phosphorylase Streptomyces coelicolor (Sco) GlgEI-V279S which plays a role in alpha-glucan biosynthesis. Sco GlgEI-V279S serves as a model enzyme for validated anti-tuberculosis (TB) target Mycobacterium tuberculosis (Mtb) GlgE. Pyrrolidine inhibitors 5 and 6 were designed based on transition state considerations and incorporate a phosphonate on the pyrrolidine moiety to expand the interaction network between the inhibitor and the enzyme active site. Compounds 5 and 6 inhibited Sco GlgEI-V279S with Ki = 45 +/- 4 muM and 95 +/- 16 muM, respectively, and crystal structures of Sco GlgE-V279S-5 and Sco GlgE-V279S-6 were obtained at a 3.2 A and 2.5 A resolution, respectively. Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like phosphorylase Streptomyces coelicolor GlgEI-V279S.,Veleti SK, Petit C, Ronning DR, Sucheck SJ Org Biomol Chem. 2017 May 10;15(18):3884-3891. doi: 10.1039/c7ob00388a. PMID:28422240[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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