Literature summary for 5.1.3.14 extracted from

Xu, Y.; Brenning, B.; Clifford, A.; Vollmer, D.; Bearss, J.; Jones, C.; McCarthy, V.; Shi, C.; Wolfe, B.; Aavula, B.; Warner, S.; Bearss, D.J.; McCullar, M.V.; Schuch, R.; Pelzek, A.; Bhaskaran, S.S.; Stebbins, C.E.; Goldberg, A.R.; Fischetti, V.A.; Vankayalapati, H.
Discovery of novel putative inhibitors of UDP-GlcNAc 2-epimerase as potent antibacterial agents (2013), ACS Med. Chem. Lett., 4, 1142-1147.

Application

Application	Comment	Organism
drug development	the enzyme is a target for development of antibiotic agent for treatment of infections caused by Gram-positive bacteria, such as Staphylococcus aureus and Bacillus anthracis	Bacillus anthracis
drug development	the enzyme is a target for development of antibiotic agent for treatment of infections caused by Gram-positive bacteria, such as Staphylococcus aureus and Bacillus anthracis	Staphylococcus aureus

Inhibitors

Inhibitors	Comment	Organism
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanamide	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanamide	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	i.e. Epimerox, 2-epimerase inhibition through a target-specific mechanism, in vivo efficacy against Staphylococcus aureus and Bacillus anthracis	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	i.e. Epimerox, 2-epimerase inhibition through a target-specific mechanism, in vivo efficacy against Staphylococcus aureus and Bacillus anthracis	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]butanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(3,5-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3,5-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3-chloro-4-methoxyphenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-bromo-3-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-bromophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-bromophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-bromophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-bromophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-chlorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-fluorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-fluorophenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-iodophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-iodophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-4-[[5-(4-methoxyphenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-4-[[5-(4-methoxyphenyl)thiophen-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-5-oxo-2-thioxo-4-([5-[4-(trifluoromethoxy)phenyl]furan-2-yl]methylidene)imidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-5-oxo-2-thioxo-4-([5-[4-(trifluoromethoxy)phenyl]furan-2-yl]methylidene)imidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
(2S)-2-[(4E)-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Bacillus anthracis
(2S)-2-[(4E)-5-oxo-4-[(5-phenylfuran-2-yl)methylidene]-2-thioxoimidazolidin-1-yl]-3-phenylpropanoic acid	-	Staphylococcus aureus
ethyl (2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoate	-	Staphylococcus aureus
ethyl (2S)-2-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-3-phenylpropanoates	-	Bacillus anthracis
additional information	synthesis and evaluation of specific inhibitors, overview	Bacillus anthracis
additional information	synthesis and evaluation of specific inhibitors, overview	Staphylococcus aureus
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]-1,1,1-trifluoromethanesulfonamide	-	Bacillus anthracis
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]-1,1,1-trifluoromethanesulfonamide	-	Staphylococcus aureus
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]methanesulfonamide	-	Bacillus anthracis
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]methanesulfonamide	-	Staphylococcus aureus
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propyl]methanesulfonamide	-	Bacillus anthracis
N-[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]propyl]methanesulfonamide	-	Staphylococcus aureus
[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]cyanamide	-	Bacillus anthracis
[1-[(4E)-4-[[5-(3,4-dichlorophenyl)furan-2-yl]methylidene]-5-oxo-2-thioxoimidazolidin-1-yl]-2-phenylethyl]cyanamide	-	Staphylococcus aureus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
UDP-N-acetyl-alpha-D-glucosamine	Bacillus anthracis	allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site	UDP-N-acetyl-alpha-D-mannosamine	-	r
UDP-N-acetyl-alpha-D-glucosamine	Staphylococcus aureus	allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site	UDP-N-acetyl-alpha-D-mannosamine	-	r

Organism

Organism	UniProt	Comment	Textmining
Bacillus anthracis	Q81K32	gene BA5509	-
Staphylococcus aureus	Q9REV4	MSRA strain	-

Reaction

Reaction	Comment	Organism	Reaction ID
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine	2-epimerase-catalyzed elimination and readdition of UDP to the glycal intermediate may proceed through a transition state with significant oxocarbenium ion-like character	Bacillus anthracis	a
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-mannosamine	2-epimerase-catalyzed elimination and readdition of UDP to the glycal intermediate may proceed through a transition state with significant oxocarbenium ion-like character	Staphylococcus aureus	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
UDP-N-acetyl-alpha-D-glucosamine	-	Bacillus anthracis	UDP-N-acetyl-alpha-D-mannosamine	-	r
UDP-N-acetyl-alpha-D-glucosamine	-	Staphylococcus aureus	UDP-N-acetyl-alpha-D-mannosamine	-	r
UDP-N-acetyl-alpha-D-glucosamine	allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site	Bacillus anthracis	UDP-N-acetyl-alpha-D-mannosamine	-	r
UDP-N-acetyl-alpha-D-glucosamine	allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site	Staphylococcus aureus	UDP-N-acetyl-alpha-D-mannosamine	-	r

Synonyms

Synonyms	Comment	Organism
UDP-GlcNAc 2-epimerase	-	Bacillus anthracis
UDP-GlcNAc 2-epimerase	-	Staphylococcus aureus

General Information

General Information	Comment	Organism
evolution	the bacterial UDP-GlcNAc-binding site is conserved and probably unique to the nonhydrolyzing bacterial 2-epimerases. Conservation of the allosteric site residues in the nonhydrolyzing bacterial 2-epimerases indicates that the allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site, is used exclusively by this class of bacterial enzymes	Bacillus anthracis
evolution	the bacterial UDP-GlcNAc-binding site is conserved and probably unique to the nonhydrolyzing bacterial 2-epimerases. Conservation of the allosteric site residues in the nonhydrolyzing bacterial 2-epimerases indicates that the allosteric regulatory mechanism, which involves direct interaction between one substrate molecule in the active site and another in the allosteric site, is used exclusively by this class of bacterial enzymes	Staphylococcus aureus