Literature summary for 4.3.3.7 extracted from

Shrivastava, P.; Navratna, V.; Silla, Y.; Dewangan, R.P.; Pramanik, A.; Chaudhary, S.; Rayasam, G.; Kumar, A.; Gopal, B.; Ramachandran, S.
Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues (2016), Sci. Rep., 6, 30827 .

Cloned(Commentary)

Cloned (Comment)	Organism
the dapA open reading frame is cloned in the expression vector pET28a for expression as N-terminal 6 x His-tagged protein	Mycobacterium tuberculosis

Crystallization (Commentary)

Crystallization (Comment)	Organism
micro-batch method and hanging drop vapour diffusion methods of crystallization	Mycobacterium tuberculosis

Inhibitors

Inhibitors	Comment	Organism
2-(4-carbamoylphenyl)-2-oxoacetic acid	maximal inhibition of 15% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
2-hydroxyheptanediamide	maximal inhibition of 21% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
2-hydroxyheptanedioic acid	maximal inhibition of 74% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
2-oxohexanedioic acid	maximal inhibition of 40% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
2-oxopentanedioic acid	maximal inhibition of 15% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
2-oxopimelate	maximal inhibition of 88% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase. This assay is able to measure DapA enzyme kinetics if the dihydrodipicolinate reductase DapB is present in excess, because under these conditions DapA becomes rate limiting	Mycobacterium tuberculosis
2-phenoxyacetic acid	maximal inhibition of 4% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-((2-amino-2-oxoethyl)sulfonyl) butanoic acid	maximal inhibition of 29% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-((2-amino-2-oxoethyl)thio)butanoic acid	maximal inhibition of 15% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-(2,4,5-trioxoimidazolidin-1-yl)butanoic acid	maximal inhibition of 21% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-amino benzoic acid	maximal inhibition of 8% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-amino-2-hydroxybenzoic acid	maximal inhibition of 4% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-[amino(oxo)acetyl]benzoic acid	maximal inhibition of 34% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-[carboxy(hydroxy)methyl]benzoic acid	maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
4-[methyl(oxalo)amino]butanoic acid	maximal inhibition of 39% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
5-(carbamoylamino)-5-oxopentanoic acid	maximal inhibition of 40% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
5-(carbamoylthio)pentanoic acid	maximal inhibition of 65% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
5-butylpyridine-2-carboxylic acid	maximal inhibition of 5% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
7-ethoxy-6,7-dioxoheptanoic acid	maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
benzoic acid	maximal inhibition of 2% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
carboxycarbonyl-benzoic acid	maximal inhibition of 22% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
ethyl 4-((2-amino-2-oxoethyl)sulfinyl)butanoate	maximal inhibition of 31% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
ethyl 4-((2-amino-2-oxoethyl)sulfonyl)butanoate	maximal inhibition of 12% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
ethyl 4-((2-amino-2-oxoethyl)thio)butanoate	maximal inhibition of 21% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
ethyl 5-(carbamoylsulfanyl)pentanoate	maximal inhibition of 34% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
ethyl [(4-amino-4-oxobutyl)(methyl)amino](oxo)acetate	maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
heptanedioic acid	maximal inhibition of 10% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
hydroxy[4-(methoxycarbonyl)phenyl]acetic acid	maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methoxycarbonyl-phenyloxoacetic acid	maximal inhibition of 29% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 3-oxohexanoate	maximal inhibition of 5% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 4-(2,4,5-trioxoimidazolidin-1-yl)butanoate	maximal inhibition of 38% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 4-[(2-ethoxy-2-oxoethyl)(methyl)amino]butanoate	maximal inhibition of 42% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 4-[amino(oxo)acetyl]benzoate	maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 5-(carbamoylamino)-5-oxopentanoate	maximal inhibition of 65% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 6-oxo-6-(2H-tetrazol-5-yl)hexanoate	maximal inhibition of 35% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 7-amino-6,7-dioxoheptanoate	maximal inhibition of 24% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
methyl 7-amino-6-hydroxy-7-oxoheptanoate	maximal inhibition of 28% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
additional information	molecular descriptors analysis shows that ligands with polar surface area of 91.7 A are likely inhibitors	Mycobacterium tuberculosis
N1-(4-amino-4-oxobutyl)-N1-methylethanediamide	maximal inhibition of 40% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis
[(4-amino-4-oxobutyl)(methyl)amino](oxo)acetic acid	maximal inhibition of 44% (highest inhibition achieved relative to that in absence of inhibitor by varying the concentration of the inhibitor at a given concentration of other substrates pyruvate 0.5 mM and 0.4 mM L-aspartate-4-semialdehyde), in a coupled assay with recombinant dihydrodipicolinate reductase	Mycobacterium tuberculosis

Organism

Organism	UniProt	Comment	Textmining
Mycobacterium tuberculosis	P9WP25	-	-
Mycobacterium tuberculosis H37Rv	P9WP25	-	-

Purification (Commentary)

Purification (Comment)	Organism
-	Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
pyruvate + L-aspartate-4-semialdehyde	-	Mycobacterium tuberculosis	(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O	-	?
pyruvate + L-aspartate-4-semialdehyde	-	Mycobacterium tuberculosis H37Rv	(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O	-	?

Synonyms

Synonyms	Comment	Organism
DapA	-	Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.021	-	2-oxopimelate	pH 7.4, 37°C	Mycobacterium tuberculosis

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.0325	-	pH 7.4, 37°C	Mycobacterium tuberculosis	2-oxopimelate