Sandbox Reserved 1476
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{{CHEM_4923_Fall2018}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | {{CHEM_4923_Fall2018}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | ||
| - | + | This page is reserved for Magan Wurth. | |
==PDB ID 3AIE== | ==PDB ID 3AIE== | ||
| - | This enzyme is | + | This enzyme is one type of glucansucrase from ''Streptococcus mutans''.<ref name="Ito">PMID:21354427</ref> These enzymes are large and extracellularly expressed by few other bacterial species.<ref name="Leemhuis">PMID:22796091</ref> Their main function is to catalyze the production of glucose polymers from sucrose substrates.<ref name="Ito" /> These polymers comprise the dental plaque that promotes tooth decay in humans. For this reason, knowledge of the structure and function of this enzyme is critical for the development of an inhibitor in an effort to reduce the prevalence of cavities and periodontal disease. |
<StructureSection load='3aie' size='350' side='right' caption='GTF-SI of Streptococcus mutans (PDB entry [[3aie]])' scene=''> | <StructureSection load='3aie' size='350' side='right' caption='GTF-SI of Streptococcus mutans (PDB entry [[3aie]])' scene=''> | ||
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==Structure== | ==Structure== | ||
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This enzyme features two well-known motifs. Domain A consists of a TIM barrel.<ref name="Ito" /> 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.<ref name="Leemhuis" /> | This enzyme features two well-known motifs. Domain A consists of a TIM barrel.<ref name="Ito" /> 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.<ref name="Leemhuis" /> | ||
| - | == Function == | ||
| - | The major functions of this enzyme include synthesis of glucan, a glucosylated acceptor molecule, or release of free glucose.<ref name="Monchois">PMID:10234842</ref> [[Image:Reaction GSase.png|thumb|Reactions catalyzed by 3aie, mutansucrase of S. mutans. Image adapted from Monchois, et.al.]] As shown in Figure 1, all of the products are released from the same active site and from a glucosyl-enzyme intermediate.<ref name="Monchois" /> The sole, natural substrate for this enzyme is sucrose.<ref name="Hamada">PMID:6446023</ref> No cofactors or energy-carriers are required for these reactions.<ref name="Monchois" /> The energy required for bond formation is solely provided by the energy released from sucrose hydrolysis.<ref name="Monchois" />This particular glucansucrase is a mutansucrase, meaning it catalyzes the formation of α(1,3) linked glucose moieties.<ref name="Ito" /> The latest research proposes that the glucose moieties are most likely added to the non-reducing end of the glucan chain.<ref name="Moulis">PMID:16864576</ref> Binding of a glucan chain to the active site may cause a conformational change within the enzyme that favors elongation of the glucan chain instead of the formation of the other products.<ref name="Monchois" /> Acceptor molecules include maltose and isomaltose.<ref name="Leemhuis" /> Free glucose may be released upon hydrolysis of the glucose-enzyme intermediate.<ref name="Leemhuis" /> | ||
| - | == | + | == Function and Energetics == |
| - | + | The major functions of this enzyme include synthesis of glucan, a glucosylated acceptor molecule, or release of free glucose.<ref name="Monchois">PMID:10234842</ref> [[Image:Reaction GSase.png|thumb|Reactions catalyzed by 3aie, mutansucrase of S. mutans. Image adapted from Monchois, et al.]] As shown in Figure 1, all of the products are released from the same active site and from a glucosyl-enzyme intermediate.<ref name="Monchois" /> The sole, natural substrate for this enzyme is sucrose.<ref name="Hamada">PMID:6446023</ref> No cofactors or energy-carriers are required for these reactions.<ref name="Monchois" /> The energy required for bond formation is solely provided by the energy released from sucrose hydrolysis.<ref name="Monchois" />This particular glucansucrase is a mutansucrase, meaning it catalyzes the formation of α(1,3) linked glucose moieties.<ref name="Ito" /> The latest research proposes that the glucose moieties are most likely added to the non-reducing end of the glucan chain.<ref name="Moulis">PMID:16864576</ref> Binding of a glucan chain to the active site may cause a conformational change within the enzyme that favors elongation of the glucan chain instead of the formation of the other products.<ref name="Monchois" /> Acceptor molecules include maltose and isomaltose.<ref name="Leemhuis" /> Free glucose may be released upon hydrolysis of the glucose-enzyme intermediate.<ref name="Leemhuis" /> | |
| - | + | == Disease and Relevance == | |
| + | As mentioned previously, one of the products of this enzyme is glucan. This glucose polymer comprises the biofilm, which plays a particularly important role in the formation of cavities.<ref name="Hamada" /> The sticky glucan helps to adhere ''S. mutans'' and other bacteria to the tooth surface, where acids can penetrate and degrade the tooth due to this localization.<ref name="Hamada" /> In fact, Hamada, et al state that the primary product of this enzyme comes from the fermentation of sucrose to yield lactic acid. Based on the activity of this enzyme, it appears to be a good candidate for inhibition. | ||
| + | Using the crystal structure of this enzyme bound to known inhibitor acarbose (PDB entry: 3aic), Zhang et al were able to create several competitive inhibitors.<ref name="Zhang">PMID:28729722</ref> Two of the inhibitors were found to be highly selective for this enzyme and reduced glucan production to 15% of the wild-type activity in rats. | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
| This Sandbox is Reserved from November 5 2018 through January 1, 2019 for use in the course "CHEM 4923: Senior Project taught by Christina R. Bourne at the University of Oklahoma, Norman, USA. This reservation includes Sandbox Reserved 1471 through Sandbox Reserved 1478. |
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This page is reserved for Magan Wurth.
PDB ID 3AIE
This enzyme is one type of glucansucrase from Streptococcus mutans.[1] These enzymes are large and extracellularly expressed by few other bacterial species.[2] Their main function is to catalyze the production of glucose polymers from sucrose substrates.[1] These polymers comprise the dental plaque that promotes tooth decay in humans. For this reason, knowledge of the structure and function of this enzyme is critical for the development of an inhibitor in an effort to reduce the prevalence of cavities and periodontal disease.
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