Literature summary for 6.3.2.9 extracted from

Sosic, I.; Barreteau, H.; Simcic, M.; Sink, R.; Cesar, J.; Zega, A.; Grdadolnik, S.G.; Contreras-Martel, C.; Dessen, A.; Amoroso, A.; Joris, B.; Blanot, D.; Gobec, S.
Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of D-glutamic acid (2011), Eur. J. Med. Chem., 46, 2880-2894.

Crystallization (Commentary)

Crystallization (Comment)	Organism
in complex with inhibitor 4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid. Only one stereoisomer is seen in the co-crystal structure. The absolute configuration of the crystallised compound is (1R,3R,4S).The carboxyl groups at positions 1 and 3 of the rigid cyclohexyl mimetic of D-glutamic acid occupy exactly the same position as the carboxyl groups of the product UDP-MurNAc-L-Ala-D-Glu. The carboxyl group at position 3 of the cyclohexyl ring of the inhibitor forms a charge-based interaction with N of Lys348, and is additionally hydrogen-bonded with a conserved water molecule, W38, which is further hydrogen-bonded to Ogamma of Thr321 and the carboxyl group of Asp182. The carboxyl group at position 1 of the cyclohexyl ring is held in place by hydrogen bonds with Ogamma of Ser415 and the backbone nitrogen of Phe422. The sulfonic group makes hydrogen bonds with His183 and water molecules W183, W242 and W415	Escherichia coli

Crystallization (Comment)

Organism

in complex with inhibitor 4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid. Only one stereoisomer is seen in the co-crystal structure. The absolute configuration of the crystallised compound is (1R,3R,4S).The carboxyl groups at positions 1 and 3 of the rigid cyclohexyl mimetic of D-glutamic acid occupy exactly the same position as the carboxyl groups of the product UDP-MurNAc-L-Ala-D-Glu. The carboxyl group at position 3 of the cyclohexyl ring of the inhibitor forms a charge-based interaction with N of Lys348, and is additionally hydrogen-bonded with a conserved water molecule, W38, which is further hydrogen-bonded to Ogamma of Thr321 and the carboxyl group of Asp182. The carboxyl group at position 1 of the cyclohexyl ring is held in place by hydrogen bonds with Ogamma of Ser415 and the backbone nitrogen of Phe422. The sulfonic group makes hydrogen bonds with His183 and water molecules W183, W242 and W415

Escherichia coli

Inhibitors

Inhibitors	Comment	Organism
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]-5-hydroxybenzoic acid	-	Escherichia coli
2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,4-dicarboxylic acid	-	Escherichia coli
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,3-dicarboxylic acid	-	Escherichia coli
4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid	-	Escherichia coli

Organism

Organism	UniProt	Comment	Textmining
Escherichia coli	P14900	-	-

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.0058	-	4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,3-dicarboxylic acid	pH 8.6, 37°C	Escherichia coli
0.026	-	2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,4-dicarboxylic acid	pH 8.6, 37°C	Escherichia coli
0.032	-	2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]-5-hydroxybenzoic acid	pH 8.6, 37°C	Escherichia coli
0.125	-	4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid	pH 8.6, 37°C	Escherichia coli

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.0084	-	pH 8.6, 37°C	Escherichia coli	4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,3-dicarboxylic acid
0.038	-	pH 8.6, 37°C	Escherichia coli	2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]benzene-1,4-dicarboxylic acid
0.046	-	pH 8.6, 37°C	Escherichia coli	2-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]-5-hydroxybenzoic acid
0.182	-	pH 8.6, 37°C	Escherichia coli	4-[([6-[(4-cyano-2-fluorobenzyl)oxy]naphthalen-2-yl]sulfonyl)amino]cyclohexane-1,3-dicarboxylic acid