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Structure and action of the C-C bond-forming glycosyltransferase UrdGT2 involved in the biosynthesis of the antibiotic urdamycin.

Mittler M, Bechthold A, Schulz GE
J Mol Biol 372 67-76 (2007)
Cited: 53 times
EuropePMC logo PMID: 17640665

Abstract

The glycosyltransferase UrdGT2 from Streptomyces fradiae catalyzes the formation of a glycosidic C-C bond between a polyketide aglycone and D-olivose. The enyzme was expressed in Escherichia coli, purified and crystallized. Its structure was established by X-ray diffraction at 1.9 A resolution. It is the first structure of a C-glycosyltransferase. UrdGT2 belongs to the structural family GT-B of the glycosyltransferases and is likely to form a C(2)-symmetric dimer in solution. The binding structures of donor and acceptor substrates in five structurally homologous enzymes provided a clear and consistent guide for the substrate-binding structure in UrdGT2. The modeled substrate locations suggest the deeply buried Asp137 as the activator for C-C bond formation and explain the reaction. The putative model can be used to design mutations that change the substrate specificity. Such mutants are of great interest in overcoming the increasing danger of antibiotic resistance.

Reviews - 2p6p mentioned but not cited (4)

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Articles - 2p6p mentioned but not cited (7)

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Reviews citing this publication (12)

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Articles citing this publication (30)

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  4. Crystal structures of glycosyltransferase UGT78G1 reveal the molecular basis for glycosylation and deglycosylation of (iso)flavonoids. Modolo LV, Li L, Pan H, Blount JW, Dixon RA, Wang X. J. Mol. Biol. 392 1292-1302 (2009)
  5. Engineering a function into a glycosyltransferase. Krauth C, Fedoryshyn M, Schleberger C, Luzhetskyy A, Bechthold A. Chem. Biol. 16 28-35 (2009)
  6. Structure and mechanism of the lipooligosaccharide sialyltransferase from Neisseria meningitidis. Lin LY, Rakic B, Chiu CP, Lameignere E, Wakarchuk WW, Withers SG, Strynadka NC. J. Biol. Chem. 286 37237-37248 (2011)
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  9. Functional characterization and substrate specificity of spinosyn rhamnosyltransferase by in vitro reconstitution of spinosyn biosynthetic enzymes. Chen YL, Chen YH, Lin YC, Tsai KC, Chiu HT. J. Biol. Chem. 284 7352-7363 (2009)
  10. Purification, molecular cloning and functional characterization of flavonoid C-glucosyltransferases from Fagopyrum esculentum M. (buckwheat) cotyledon. Nagatomo Y, Usui S, Ito T, Kato A, Shimosaka M, Taguchi G. Plant J. 80 437-448 (2014)
  11. Heterologous expression and manipulation of three tetracycline biosynthetic pathways. Wang P, Kim W, Pickens LB, Gao X, Tang Y. Angew. Chem. Int. Ed. Engl. 51 11136-11140 (2012)
  12. Engineering and kinetic characterisation of two glucosyltransferases from Arabidopsis thaliana. Weis M, Lim EK, Bruce NC, Bowles DJ. Biochimie 90 830-834 (2008)
  13. Biosynthetic pathway toward carbohydrate-like moieties of alnumycins contains unusual steps for C-C bond formation and cleavage. Oja T, Klika KD, Appassamy L, Sinkkonen J, Mäntsälä P, Niemi J, Metsä-Ketelä M. Proc. Natl. Acad. Sci. U.S.A. 109 6024-6029 (2012)
  14. Bacterial Glycosyltransferases: Challenges and Opportunities of a Highly Diverse Enzyme Class Toward Tailoring Natural Products. Schmid J, Heider D, Wendel NJ, Sperl N, Sieber V. Front Microbiol 7 182 (2016)
  15. Identification and functional analysis of 2-hydroxyflavanone C-glucosyltransferase in soybean (Glycine max). Hirade Y, Kotoku N, Terasaka K, Saijo-Hamano Y, Fukumoto A, Mizukami H. FEBS Lett. 589 1778-1786 (2015)
  16. Modulation of deoxysugar transfer by the elloramycin glycosyltransferase ElmGT through site-directed mutagenesis. Ramos A, Olano C, Braña AF, Méndez C, Salas JA. J. Bacteriol. 191 2871-2875 (2009)
  17. Crystal structure of the glycosyltransferase SnogD from the biosynthetic pathway of nogalamycin in Streptomyces nogalater. Claesson M, Siitonen V, Dobritzsch D, Metsä-Ketelä M, Schneider G. FEBS J. 279 3251-3263 (2012)
  18. Structural basis for C-ribosylation in the alnumycin A biosynthetic pathway. Oja T, Niiranen L, Sandalova T, Klika KD, Niemi J, Mäntsälä P, Schneider G, Metsä-Ketelä M. Proc. Natl. Acad. Sci. U.S.A. 110 1291-1296 (2013)
  19. Structural studies of the spinosyn forosaminyltransferase, SpnP. Isiorho EA, Jeon BS, Kim NH, Liu HW, Keatinge-Clay AT. Biochemistry 53 4292-4301 (2014)
  20. Differences in the substrate specificity of glycosyltransferases involved in landomycins A and E biosynthesis. Erb A, Krauth C, Luzhetskyy A, Bechthold A. Appl. Microbiol. Biotechnol. 83 1067-1076 (2009)
  21. Pseudouridine monophosphate glycosidase: a new glycosidase mechanism. Huang S, Mahanta N, Begley TP, Ealick SE. Biochemistry 51 9245-9255 (2012)
  22. The C-glycosyltransferase IroB from pathogenic Escherichia coli: identification of residues required for efficient catalysis. Foshag D, Campbell C, Pawelek PD. Biochim. Biophys. Acta 1844 1619-1630 (2014)
  23. Molecular characterization of the C-glucosylation for puerarin biosynthesis in Pueraria lobata. Wang X, Li C, Zhou C, Li J, Zhang Y. Plant J. 90 535-546 (2017)
  24. In vivo investigation of the substrate recognition capability and activity affecting amino acid residues of glycosyltransferase FscMI in the biosynthesis of candicidin. Lei X, Kong L, Zhang C, Liu Q, Yao F, Zhang W, Deng Z, You D. Mol Biosyst 9 422-430 (2013)
  25. Elucidation of the glycosylation steps during biosynthesis of antitumor macrolides PM100117 and PM100118 and engineering for novel derivatives. Salcedo RG, Olano C, Fernández R, Braña AF, Méndez C, de la Calle F, Salas JA. Microb. Cell Fact. 15 187 (2016)
  26. Enzymatic Synthesis of Acylphloroglucinol 3-C-Glucosides from 2-O-Glucosides using a C-Glycosyltransferase from Mangifera indica. Chen D, Sun L, Chen R, Xie K, Yang L, Dai J. Chemistry 22 5873-5877 (2016)
  27. Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria. Ouchene R, Stien D, Segret J, Kecha M, Rodrigues AMS, Veckerlé C, Suzuki MT. Front Microbiol 13 906161 (2022)
  28. OleD Loki as a Catalyst for Hydroxamate Glycosylation. Hughes RR, Shaaban KA, Ponomareva LV, Horn J, Zhang C, Zhan CG, Voss SR, Leggas M, Thorson JS. Chembiochem 21 952-957 (2020)
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  30. Structural mechanism of a dual-functional enzyme DgpA/B/C as both a C-glycoside cleaving enzyme and an O- to C-glycoside isomerase. He P, Wang S, Li S, Liu S, Zhou S, Wang J, Tao J, Wang D, Wang R, Ma W. Acta Pharm Sin B 13 246-255 (2023)


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