Sandbox Reserved 1476

Structure

The structure at right can be organized into both broad regions and more defined domains. There are three main regions: N-terminal region, catalytic region, and C-terminal glucan binding region.^[1] The domains are more complex. There are five total domains; however, only four are visible in this crystal structure. Each domain consists of an N-terminal and C-terminal portion of the polypeptide chain, except Domain C, which is located at the bottom of the enzyme.^[1] Following the polypeptide chain from N-terminus to C-terminus would pass through the domains in the following order: V, IV, B, A, C, A, B, IV, V.^[2] A high degree of structural similarity exists within the GH70 family enzymes.^[2]

Catalytic Domain

Domain A is regarded as the catalytic domain.^[1] Within it, exists a highly conserved , which includes two aspartic acid residues and a general acid/base glutamate.^[1] A calcium ion is also bound to help stabilize the formation of the catalytic domain.^[1]

Supersecondary Structure

This enzyme features two well-known motifs. Domain A consists of a TIM barrel.^[1] It is composed of a ring of beta strands surrounded by a ring of alpha helices. Domain C contains a greek key motif, which is four antiparallel beta strands that form a sheet.^[2]

Function

The major functions of this enzyme include synthesis of glucan, a glucosylated acceptor molecule, or release of free glucose.^[3] All of the various products are released from the same active site and from a glucose-enzyme intermediate.^[1] The sole natural donor for all of these reactions is sucrose.^[4] No cofactors or energy-carriers are required for these reactions.^[3] The energy required for bond formation is solely provided by the energy released from sucrose hydrolysis.^[3]This particular glucansucrase is a mutansucase, which catalyzes the formation of alpha (1,3) linked glucose moieties.^[1] The latest research proposes that the glucose moieties are most likely added to the non-reducing end of the glucan chain.^[5]

Disease

Relevance

Based on the enzyme's contributions to dental cavity formation, this enzyme and its genes are attractive targets for inhibition.

References

1. ↑ ^{1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9} Ito K, Ito S, Shimamura T, Weyand S, Kawarasaki Y, Misaka T, Abe K, Kobayashi T, Cameron AD, Iwata S. Crystal Structure of Glucansucrase from the Dental Caries Pathogen Streptococcus mutans. J Mol Biol. 2011 Feb 25. PMID:21354427 doi:10.1016/j.jmb.2011.02.028
2. ↑ ^{2.0 2.1 2.2 2.3} Leemhuis H, Pijning T, Dobruchowska JM, van Leeuwen SS, Kralj S, Dijkstra BW, Dijkhuizen L. Glucansucrases: three-dimensional structures, reactions, mechanism, alpha-glucan analysis and their implications in biotechnology and food applications. J Biotechnol. 2013 Jan 20;163(2):250-72. doi: 10.1016/j.jbiotec.2012.06.037. Epub, 2012 Jul 10. PMID:22796091 doi:http://dx.doi.org/10.1016/j.jbiotec.2012.06.037
3. ↑ ^{3.0 3.1 3.2} Monchois V, Willemot RM, Monsan P. Glucansucrases: mechanism of action and structure-function relationships. FEMS Microbiol Rev. 1999 Apr;23(2):131-51. doi:, 10.1111/j.1574-6976.1999.tb00394.x. PMID:10234842 doi:http://dx.doi.org/10.1111/j.1574-6976.1999.tb00394.x
4. ↑ Hamada S, Slade HD. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev. 1980 Jun;44(2):331-84. PMID:6446023
5. ↑ Moulis C, Joucla G, Harrison D, Fabre E, Potocki-Veronese G, Monsan P, Remaud-Simeon M. Understanding the polymerization mechanism of glycoside-hydrolase family 70 glucansucrases. J Biol Chem. 2006 Oct 20;281(42):31254-67. doi: 10.1074/jbc.M604850200. Epub 2006, Jul 24. PMID:16864576 doi:http://dx.doi.org/10.1074/jbc.M604850200