Literature summary for 6.3.1.12 extracted from

Skedelj, V.; Perdih, A.; Brvar, M.; Kroflic, A.; Dubbee, V.; Savage, V.; O'Neill, A.J.; Solmajer, T.; Bester-Rogac, M.; Blanot, D.; Hugonnet, J.E.; Magnet, S.; Arthur, M.; Mainardi, J.L.; Stojan, J.; Zega, A.
Discovery of the first inhibitors of bacterial enzyme D-aspartate ligase from Enterococcus faecium (Aslfm) (2013), Eur. J. Med. Chem., 67, 208-220.

Application

Application	Comment	Organism
drug development	D-aspartate ligase of Enterococcus faecium is an attractive target for the development of narrow-spectrum antibacterial agents that are active against multidrug-resistant Enterococcus faecium	Enterococcus faecium

Cloned(Commentary)

Cloned (Comment)	Organism
His-tagged enzyme expression in Escherichia coli strain BL21 (lDE3)/pREP4	Enterococcus faecium

Inhibitors

Inhibitors	Comment	Organism
1-(4-methylphenyl)-5-[5-(3-methylphenyl)-1H-pyrazol-4-yl]-1H-tetrazole	-	Enterococcus faecium
1H-imidazol-4-yl(diphenyl)methanol	-	Enterococcus faecium
2-amino-N,N-bis(pyridin-2-ylmethyl)oxazole-5-carboxamide	-	Enterococcus faecium
2-amino-N,N-dibenzyl-4-methylthiazole-5-carboxamide	-	Enterococcus faecium
2-amino-N,N-dibenzyloxazole-5-carboxamide	-	Enterococcus faecium
2-amino-N,N-dibenzylthiazole-5-carboxamide	-	Enterococcus faecium
2-amino-N,N-dibutyloxazole-5-carboxamide	-	Enterococcus faecium
2-amino-N-(1H-benzo[d]imidazol-2-yl)oxazole-5-carboxamide	-	Enterococcus faecium
2-amino-N-benzyl-N-butyloxazole-5-carboxamide	-	Enterococcus faecium
2-amino-N-ethyl-N-(pyridin-4-ylmethyl)oxazole-5-carboxamide	-	Enterococcus faecium
2-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1H-benzimidazol-1-yl]-N-methyl-N-phenylacetamide	-	Enterococcus faecium
2-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1H-benzimidazol-1-yl]-N-phenylacetamide	-	Enterococcus faecium
2-[2-[(methylsulfonyl)amino]-1,3-thiazol-4-yl]-N,N-bis(thiophen-2-ylmethyl)acetamide	-	Enterococcus faecium
4-phenyl-5-(1-phenyl-1H-tetrazol-5-yl)pyrimidin-2-amine	-	Enterococcus faecium
5-(diphenylphosphoryl)-1,3,4-thiadiazol-2-amine	-	Enterococcus faecium
6-[(2,4-dichlorobenzyl)sulfanyl]-9H-purin-2-amine	-	Enterococcus faecium
6-[(2,6-dichlorobenzyl)sulfanyl]-9H-purin-2-amine	-	Enterococcus faecium
additional information	screening of a series of amino-oxazoles derived from bacterial biotin carboxylase inhibitors, the compounds show low micromolar activity against D-aspartate ligase. Screening of enzyme inhibitors with 7-amino-9H-purine and 7-amino-1H-pyrazolo[3,4-d]pyrimidine scaffolds, the compounds are competitive with respect to the ATP molecule	Enterococcus faecium
N,N-dibenzyl-9H-purin-6-amine	-	Enterococcus faecium
N-((1H-indol-5-yl)methyl)-2-amino-N-(3,5-dibromobenzyl)oxazole-5-carboxamide	-	Enterococcus faecium
N-((1H-indol-5-yl)methyl)-2-aminooxazole-5-carboxamide	-	Enterococcus faecium
N-(furan-2-ylmethyl)-5-hydroxy-N-(thiophen-2-ylmethyl)pyrazine-2-carboxamide	-	Enterococcus faecium
N-(furan-2-ylmethyl)-6-hydroxy-N-(thiophen-2-ylmethyl)pyridine-3-carboxamide	-	Enterococcus faecium
N-benzyl-N-(2,6-dichlorobenzyl)-9H-purin-6-amine	-	Enterococcus faecium
N-benzyl-N-(4-chlorobenzyl)-9H-purin-6-amine	-	Enterococcus faecium
N4-(2,3-dichlorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N4-(2,4-dichlorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N4-(2,4-difluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N4-(2,6-difluoro-3-methylbenzyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N4-(2,6-difluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N4-(2-chloro-6-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N4-[(2-chloropyridin-3-yl)methyl]-N4-methyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N4-[(5-chlorothiophen-2-yl)methyl]-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine	-	Enterococcus faecium
N6-(1,3-benzodioxol-5-ylmethyl)-9H-purine-2,6-diamine	-	Enterococcus faecium
N6-(2,4-dichlorobenzyl)-9H-purine-2,6-diamine	-	Enterococcus faecium
N6-(2,4-dimethoxybenzyl)-9H-purine-2,6-diamine	-	Enterococcus faecium
N6-(3,4-dichlorobenzyl)-9H-purine-2,6-diamine	-	Enterococcus faecium

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + D-aspartate + [beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n	Enterococcus faecium	-	[beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-6-N-(beta-D-Asp)-L-Lys-D-Ala-D-Ala)]n + ADP + phosphate	-	?
ATP + D-aspartate + [beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n	Enterococcus faecium D359	-	[beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-6-N-(beta-D-Asp)-L-Lys-D-Ala-D-Ala)]n + ADP + phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Enterococcus faecium	-	-	-
Enterococcus faecium D359	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21 (lDE3)/pREP4 by nickel affinity chromatography, gel filtration, and ultrafiltration	Enterococcus faecium

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + D-aspartate + [beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n	-	Enterococcus faecium	[beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-6-N-(beta-D-Asp)-L-Lys-D-Ala-D-Ala)]n + ADP + phosphate	-	?
ATP + D-aspartate + [beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n	-	Enterococcus faecium D359	[beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-6-N-(beta-D-Asp)-L-Lys-D-Ala-D-Ala)]n + ADP + phosphate	-	?

Synonyms

Synonyms	Comment	Organism
Aslfm	-	Enterococcus faecium

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Enterococcus faecium

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
8	-	assay at	Enterococcus faecium

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Enterococcus faecium

General Information

General Information	Comment	Organism
evolution	the enzyme belongs to the ATP-grasp superfamily	Enterococcus faecium