Crystal structure of glucansucrase from the dental caries pathogen Streptococcus mutans

J Mol Biol. 2011 Apr 29;408(2):177-86. doi: 10.1016/j.jmb.2011.02.028. Epub 2011 Feb 25.


Glucansucrase (GSase) from Streptococcus mutans is an essential agent in dental caries pathogenesis. Here, we report the crystal structure of S. mutans glycosyltransferase (GTF-SI), which synthesizes soluble and insoluble glucans and is a glycoside hydrolase (GH) family 70 GSase in the free enzyme form and in complex with acarbose and maltose. Resolution of the GTF-SI structure confirmed that the domain order of GTF-SI is circularly permuted as compared to that of GH family 13 α-amylases. As a result, domains A, B and IV of GTF-SI are each composed of two separate polypeptide chains. Structural comparison of GTF-SI and amylosucrase, which is closely related to GH family 13 amylases, indicated that the two enzymes share a similar transglycosylation mechanism via a glycosyl-enzyme intermediate in subsite -1. On the other hand, novel structural features were revealed in subsites +1 and +2 of GTF-SI. Trp517 provided the platform for glycosyl acceptor binding, while Tyr430, Asn481 and Ser589, which are conserved in family 70 enzymes but not in family 13 enzymes, comprised subsite +1. Based on the structure of GTF-SI and amino acid comparison of GTF-SI, GTF-I and GTF-S, Asp593 in GTF-SI appeared to be the most critical point for acceptor sugar orientation, influencing the transglycosylation specificity of GSases, that is, whether they produced insoluble glucan with α(1-3) glycosidic linkages or soluble glucan with α(1-6) linkages. The structural information derived from the current study should be extremely useful in the design of novel inhibitors that prevent the biofilm formation by GTF-SI.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Dental Caries / enzymology*
  • Dental Caries / microbiology
  • Dental Caries / pathology
  • Glucans / metabolism
  • Glucosyltransferases / chemistry
  • Glucosyltransferases / metabolism
  • Glycosylation
  • Glycosyltransferases / chemistry*
  • Glycosyltransferases / metabolism
  • Humans
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Streptococcus mutans / enzymology*


  • Glucans
  • Glycosyltransferases
  • Glucosyltransferases
  • alternansucrase
  • amylosucrase

Associated data

  • PDB/3AIC
  • PDB/3AIE