3rhz Citations

Structural and functional analysis of a new subfamily of glycosyltransferases required for glycosylation of serine-rich streptococcal adhesins.

J Biol Chem 286 27048-57 (2011)
Cited: 24 times
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Abstract

Serine-rich repeat glycoproteins (SRRPs) are a growing family of bacterial adhesins found in many streptococci and staphylococci; they play important roles in bacterial biofilm formation and pathogenesis. Glycosylation of this family of adhesins is essential for their biogenesis. A glucosyltransferase (Gtf3) catalyzes the second step of glycosylation of a SRRP (Fap1) from an oral streptococcus, Streptococcus parasanguinis. Although Gtf3 homologs are highly conserved in SRRP-containing streptococci, they share minimal homology with functionally known glycosyltransferases. We report here the 2.3 Å crystal structure of Gtf3. The structural analysis indicates that Gtf3 forms a tetramer and shares significant structural homology with glycosyltransferases from GT4, GT5, and GT20 subfamilies. Combining crystal structural analysis with site-directed mutagenesis and in vitro glycosyltransferase assays, we identified residues that are required for UDP- or UDP-glucose binding and for oligomerization of Gtf3 and determined their contribution to the enzymatic activity of Gtf3. Further in vivo studies revealed that the critical amino acid residues identified by the structural analysis are crucial for Fap1 glycosylation in S. parasanguinis in vivo. Moreover, Gtf3 homologs from other streptococci were able to rescue the gtf3 knock-out mutant of S. parasanguinis in vivo and catalyze the sugar transfer to the modified SRRP substrate in vitro, demonstrating the importance and conservation of the Gtf3 homologs in glycosylation of SRRPs. As the Gtf3 homologs only exist in SRRP-containing streptococci, we conclude that the Gtf3 homologs represent a unique subfamily of glycosyltransferases.

Articles - 3rhz mentioned but not cited (1)

  1. Structural and functional analysis of a new subfamily of glycosyltransferases required for glycosylation of serine-rich streptococcal adhesins. Zhu F, Erlandsen H, Ding L, Li J, Huang Y, Zhou M, Liang X, Ma J, Wu H. J Biol Chem 286 27048-27057 (2011)


Reviews citing this publication (7)

  1. The sweet tooth of bacteria: common themes in bacterial glycoconjugates. Tytgat HL, Lebeer S. Microbiol Mol Biol Rev 78 372-417 (2014)
  2. Advances in understanding glycosyltransferases from a structural perspective. Gloster TM. Curr Opin Struct Biol 28 131-141 (2014)
  3. A role for glycosylated serine-rich repeat proteins in gram-positive bacterial pathogenesis. Lizcano A, Sanchez CJ, Orihuela CJ. Mol Oral Microbiol 27 257-269 (2012)
  4. Collagen-binding proteins of Streptococcus mutans and related streptococci. Avilés-Reyes A, Miller JH, Lemos JA, Abranches J. Mol Oral Microbiol 32 89-106 (2017)
  5. Glycosyltransferase-mediated Sweet Modification in Oral Streptococci. Zhu F, Zhang H, Wu H. J Dent Res 94 659-665 (2015)
  6. How Sweet Are Our Gut Beneficial Bacteria? A Focus on Protein Glycosylation in Lactobacillus. Latousakis D, Juge N. Int J Mol Sci 19 E136 (2018)
  7. Insights into bacterial protein glycosylation in human microbiota. Zhu F, Wu H. Sci China Life Sci 59 11-18 (2016)

Articles citing this publication (16)

  1. The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. Zhang H, Zhu F, Yang T, Ding L, Zhou M, Li J, Haslam SM, Dell A, Erlandsen H, Wu H. Nat Commun 5 4339 (2014)
  2. Engineering and Dissecting the Glycosylation Pathway of a Streptococcal Serine-rich Repeat Adhesin. Zhu F, Zhang H, Yang T, Haslam SM, Dell A, Wu H. J Biol Chem 291 27354-27363 (2016)
  3. Structure-Based Discovery of Small Molecule Inhibitors of Cariogenic Virulence. Zhang Q, Nijampatnam B, Hua Z, Nguyen T, Zou J, Cai X, Michalek SM, Velu SE, Wu H. Sci Rep 7 5974 (2017)
  4. Gap1 functions as a molecular chaperone to stabilize its interactive partner Gap3 during biogenesis of serine-rich repeat bacterial adhesin. Zhou M, Zhu F, Li Y, Zhang H, Wu H. Mol Microbiol 83 866-878 (2012)
  5. Defining the enzymatic pathway for polymorphic O-glycosylation of the pneumococcal serine-rich repeat protein PsrP. Jiang YL, Jin H, Yang HB, Zhao RL, Wang S, Chen Y, Zhou CZ. J Biol Chem 292 6213-6224 (2017)
  6. Structural and mechanistic characterization of leukocyte-type core 2 β1,6-N-acetylglucosaminyltransferase: a metal-ion-independent GT-A glycosyltransferase. Pak JE, Satkunarajah M, Seetharaman J, Rini JM. J Mol Biol 414 798-811 (2011)
  7. New Helical Binding Domain Mediates a Glycosyltransferase Activity of a Bifunctional Protein. Zhang H, Zhou M, Yang T, Haslam SM, Dell A, Wu H. J Biol Chem 291 22106-22117 (2016)
  8. Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties. Lizcano A, Akula Suresh Babu R, Shenoy AT, Saville AM, Kumar N, D'Mello A, Hinojosa CA, Gilley RP, Segovia J, Mitchell TJ, Tettelin H, Orihuela CJ. Microbes Infect 19 323-333 (2017)
  9. Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from Streptococcus gordonii. Chen Y, Bensing BA, Seepersaud R, Mi W, Liao M, Jeffrey PD, Shajahan A, Sonon RN, Azadi P, Sullam PM, Rapoport TA. J Biol Chem 293 5360-5373 (2018)
  10. A conserved domain is crucial for acceptor substrate binding in a family of glucosyltransferases. Zhu F, Zhang H, Wu H. J Bacteriol 197 510-517 (2015)
  11. Serine-rich repeat protein adhesins from Lactobacillus reuteri display strain specific glycosylation profiles. Latousakis D, Nepravishta R, Rejzek M, Wegmann U, Le Gall G, Kavanaugh D, Colquhoun IJ, Frese S, MacKenzie DA, Walter J, Angulo J, Field RA, Juge N. Glycobiology 29 45-58 (2019)
  12. Gap2 promotes the formation of a stable protein complex required for mature Fap1 biogenesis. Echlin H, Zhu F, Li Y, Peng Z, Ruiz T, Bedwell GJ, Prevelige PE, Wu H. J Bacteriol 195 2166-2176 (2013)
  13. Structural and biochemical analysis of a bacterial glycosyltransferase. Zhu F, Wu R, Zhang H, Wu H. Methods Mol Biol 1022 29-39 (2013)
  14. Biochemical characterization of a glycosyltransferase Gtf3 from Mycobacterium smegmatis: a case study of improved protein solubilization. Bakli M, Karim L, Mokhtari-Soulimane N, Merzouk H, Vincent F. 3 Biotech 10 436 (2020)
  15. NMR assignment of the amylase-binding protein A from Streptococcus parasanguinis. Liu B, Zhu F, Wu H, Matthews S. Biomol NMR Assign 9 173-175 (2015)
  16. Preliminary X-ray crystallographic studies of an N-terminal domain of unknown function from a putative glycosyltransferase from Streptococcus parasanguinis. Zhang H, Zhu F, Ding L, Zhou M, Wu R, Wu H. Acta Crystallogr Sect F Struct Biol Cryst Commun 69 520-523 (2013)