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Literature summary for 1.8.1.4 extracted from

  • Bryk, R.; Arango, N.; Venugopal, A.; Warren, J.D.; Park, Y.H.; Patel, M.S.; Lima, C.D.; Nathan, C.
    Triazaspirodimethoxybenzoyls as selective inhibitors of mycobacterial lipoamide dehydrogenase (2010), Biochemistry, 49, 1616-1627.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli BL21(DE3) Codon Plus RLI cells Mycobacterium tuberculosis

Crystallization (Commentary)

Crystallization (Comment) Organism
alone or in complex with inhibitor N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamide, hanging drop vapor diffusion method, using 100 mM Tris (pH 8.5), 10 mM NaCl, 11% (w/v) polyethylene glycol 10000, and 15% (v/v) ethylene glycol Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
A181V the mutant is not inhibited by N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid compared to the wild type enzyme Mycobacterium tuberculosis
A290R the mutant is less sensitive to N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid than the wild type enzyme Mycobacterium tuberculosis
F269R the mutant is less sensitive to N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid than the wild type enzyme Mycobacterium tuberculosis
G312A/L313G/L314P/Q315M the mutant is less sensitive to N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid than the wild type enzyme Mycobacterium tuberculosis
L314P the mutant is less sensitive to N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid than the wild type enzyme Mycobacterium tuberculosis
N209V the mutant is less sensitive to N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid than the wild type enzyme Mycobacterium tuberculosis
R147T the mutant is more sensitive to N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid than the wild type enzyme Mycobacterium tuberculosis
R347S the mutant is not inhibited by N-(2,4-dichlorophenethyl)-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro-[4.5]decan-3-yl]acetamid compared to the wild type enzyme Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-N-[3-(trifluoromethyl)benzyl]acetamide
-
Mycobacterium tuberculosis
N-[2-(2,4-dichlorophenyl)ethyl]-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]acetamide most potent inhibitor, noncompetitive versus NADH, NAD+, and lipoamide Mycobacterium tuberculosis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WHH8
-
-
Mycobacterium tuberculosis CDC 1551 P9WHH8
-
-

Purification (Commentary)

Purification (Comment) Organism
Ni-NTA-agarose resin column chromatography and Superdex 200 gel filtration Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
dihydrolipoamide + NAD+
-
Mycobacterium tuberculosis lipoamide + NADH
-
?
dihydrolipoamide + NAD+
-
Mycobacterium tuberculosis CDC 1551 lipoamide + NADH
-
?

Synonyms

Synonyms Comment Organism
lipoamide dehydrogenase
-
Mycobacterium tuberculosis
LPD
-
Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
FAD
-
Mycobacterium tuberculosis
NAD+
-
Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000865
-
N-[2-(2,4-dichlorophenyl)ethyl]-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]acetamide pH and temperature not specified in the publication Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0009
-
pH and temperature not specified in the publication Mycobacterium tuberculosis N-[2-(2,4-dichlorophenyl)ethyl]-2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]acetamide
0.002
-
pH and temperature not specified in the publication Mycobacterium tuberculosis 2-[8-(2,4-dimethoxybenzoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-N-[3-(trifluoromethyl)benzyl]acetamide