PubMed:10617596 JSONTXT

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":401,"end":412},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000521"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":317,"end":336},"obj":"Glycan_Motif"},{"id":"T2","span":{"begin":1338,"end":1345},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G64581RP"},{"id":"A2","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G15021LG"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":99},"obj":"Sentence"},{"id":"T2","span":{"begin":100,"end":146},"obj":"Sentence"},{"id":"T3","span":{"begin":147,"end":308},"obj":"Sentence"},{"id":"T4","span":{"begin":309,"end":499},"obj":"Sentence"},{"id":"T5","span":{"begin":500,"end":692},"obj":"Sentence"},{"id":"T6","span":{"begin":693,"end":805},"obj":"Sentence"},{"id":"T7","span":{"begin":806,"end":936},"obj":"Sentence"},{"id":"T8","span":{"begin":937,"end":1052},"obj":"Sentence"},{"id":"T9","span":{"begin":1053,"end":1276},"obj":"Sentence"},{"id":"T10","span":{"begin":1277,"end":1495},"obj":"Sentence"},{"id":"T11","span":{"begin":1496,"end":1822},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":317,"end":336},"obj":"https://glytoucan.org/Structures/Glycans/G64581RP"},{"id":"T2","span":{"begin":1338,"end":1345},"obj":"https://glytoucan.org/Structures/Glycans/G15021LG"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":418,"end":424},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G97099AY"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G97099AY"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":418,"end":424},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G97099AY"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G97099AY"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"GlyCosmos15-CL","denotations":[{"id":"T1","span":{"begin":401,"end":412},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000521"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"GlyCosmos15-Taxon","denotations":[{"id":"T1","span":{"begin":14,"end":30},"obj":"Organism"},{"id":"T2","span":{"begin":293,"end":300},"obj":"Organism"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"562"},{"id":"A2","pred":"db_id","subj":"T2","obj":"29189"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":401,"end":412},"obj":"Body_part"},{"id":"T2","span":{"begin":413,"end":417},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000521"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000060"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":99},"obj":"Sentence"},{"id":"T2","span":{"begin":100,"end":146},"obj":"Sentence"},{"id":"T3","span":{"begin":147,"end":308},"obj":"Sentence"},{"id":"T4","span":{"begin":309,"end":499},"obj":"Sentence"},{"id":"T5","span":{"begin":500,"end":692},"obj":"Sentence"},{"id":"T6","span":{"begin":693,"end":805},"obj":"Sentence"},{"id":"T7","span":{"begin":806,"end":936},"obj":"Sentence"},{"id":"T8","span":{"begin":937,"end":1052},"obj":"Sentence"},{"id":"T9","span":{"begin":1053,"end":1276},"obj":"Sentence"},{"id":"T10","span":{"begin":1277,"end":1495},"obj":"Sentence"},{"id":"T11","span":{"begin":1496,"end":1822},"obj":"Sentence"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":14,"end":30},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":293,"end":300},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"562"},{"id":"A2","pred":"db_id","subj":"T2","obj":"29189"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":401,"end":412},"obj":"Body_part"},{"id":"T2","span":{"begin":413,"end":417},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000521"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000060"}],"text":"Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis.\nGlucosamine-6-phosphate synthase (GlmS) catalyzes the formation of D-glucosamine 6-phosphate from D-fructose 6-phosphate using L-glutamine as the ammonia source. Because N-acetylglucosamine is an essential building block of both bacterial cell walls and fungal cell wall chitin, the enzyme is a potential target for antibacterial and antifungal agents. The most potent carbohydrate-based inhibitor of GlmS reported to date is 2-amino-2-deoxy-D-glucitol 6-phosphate, an analogue of the putative cis-enolamine intermediate formed during catalysis. The interaction of a series of structurally related cis-enolamine intermediate analogues with GlmS is described. Although arabinose oxime 5-phosphate is identified as a good competitive inhibitor of GlmS with an inhibition constant equal to 1. 2 (+/-0.3) mM, the presence of the amino function at the 2-position is shown to be important for potent inhibition. Comparison of the binding affinities of 2-deoxy-D-glucitol 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate indicates that the amino function contributes -4.1 (+/-0.1) kcal/mol to the free energy of inhibitor binding. Similarly, comparison of the binding affinities of 2-deoxy-D-glucose 6-phosphate and D-glucosamine 6-phosphate indicates that the amino function contributes -3.0 (+/-0.1) kcal/mol to the free energy of product binding. Interactions between GlmS and the 2-amino function of its ligands contribute to the uniform binding of the product and the cis-enolamine intermediate as evidenced by the similar contribution of the amino group to the free energy of binding of D-glucosamine 6-phosphate and 2-amino-2-deoxy-D-glucitol 6-phosphate, respectively."}