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Literature summary for 6.3.2.12 extracted from

  • Zhao, F.; Wang, X.D.; Erber, L.N.; Luo, M.; Guo, A.Z.; Yang, S.S.; Gu, J.; Turman, B.J.; Gao, Y.R.; Li, D.F.; Cui, Z.Q.; Zhang, Z.P.; Bi, L.J.; Baughn, A.D.; Zhang, X.E.; Deng, J.Y.
    Binding pocket alterations in dihydrofolate synthase confer resistance to para-aminosalicylic acid in clinical isolates of Mycobacterium tuberculosis (2014), Antimicrob. Agents Chemother., 58, 1479-1487.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene folC, cloning and expression of wild-type and mutant enzymes with maltose binding protein-tag linked by a factor Xa cleavage site in Escherichia coli strain BL21(DE3) Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
A183P naturally occuring conserved mutation, the mutant shows reduced enzyme activity Mycobacterium tuberculosis variant bovis
D112A naturally occuring mutation Mycobacterium tuberculosis
E153A naturally occuring conserved mutation, the mutant shows reduced enzyme activity Mycobacterium tuberculosis
E153G naturally occuring conserved mutation Mycobacterium tuberculosis
E40G naturally occuring mutation Mycobacterium tuberculosis
F152L naturally occuring conserved mutation Mycobacterium tuberculosis
F152S naturally occuring conserved mutation Mycobacterium tuberculosis
G111S naturally occuring mutation Mycobacterium tuberculosis
I43A naturally occuring mutation Mycobacterium tuberculosis
I43T naturally occuring mutation, the mutant shows reduced enzyme activity Mycobacterium tuberculosis
additional information 4-aminosalicylic acid susceptibility of mutant strains, overview Mycobacterium tuberculosis
N73S naturally occuring conserved mutation Mycobacterium tuberculosis
R410W naturally occuring mutation Mycobacterium tuberculosis
R49W naturally occuring conserved mutation, the mutant shows reduced enzyme activity Mycobacterium tuberculosis variant bovis
S150G naturally occuring conserved mutation Mycobacterium tuberculosis
S150R naturally occuring conserved mutation Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 7,8-dihydropteroate + L-glutamate Mycobacterium tuberculosis
-
ADP + phosphate + 7,8-dihydropteroylglutamate
-
?
ATP + 7,8-dihydropteroate + L-glutamate Mycobacterium tuberculosis variant bovis
-
ADP + phosphate + 7,8-dihydropteroylglutamate
-
?
ATP + 7,8-dihydropteroate + L-glutamate Mycobacterium tuberculosis H37Rv
-
ADP + phosphate + 7,8-dihydropteroylglutamate
-
?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis I6Y0R5 gene folC
-
Mycobacterium tuberculosis H37Rv I6Y0R5 gene folC
-
Mycobacterium tuberculosis variant bovis A0A0H3M8P3 gene folC
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and mutant enzymes with maltose binding protein-tag linked by a factor Xa cleavage site from Escherichia coli strain BL21(DE3) by amylose affinity chromatography, tag cleavage by faxtor Xa, dialysis, and anion exchange chromatography Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 7,8-dihydropteroate + L-glutamate
-
Mycobacterium tuberculosis ADP + phosphate + 7,8-dihydropteroylglutamate
-
?
ATP + 7,8-dihydropteroate + L-glutamate
-
Mycobacterium tuberculosis variant bovis ADP + phosphate + 7,8-dihydropteroylglutamate
-
?
ATP + 7,8-dihydropteroate + L-glutamate
-
Mycobacterium tuberculosis H37Rv ADP + phosphate + 7,8-dihydropteroylglutamate
-
?

Synonyms

Synonyms Comment Organism
FolC
-
Mycobacterium tuberculosis
FolC
-
Mycobacterium tuberculosis variant bovis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
9.5
-
assay at Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mycobacterium tuberculosis
ATP
-
Mycobacterium tuberculosis variant bovis

General Information

General Information Comment Organism
malfunction in Mycobacterium bovis clinical isolates missense mutations within the coding sequence of the folC gene cause alterations within the 7,8-dihydropteroate binding pocket resulting in 4-aminosalicylic acid resistance. The alterations in the substrate binding pocket result in reduced dihydrofolate synthase activity and abolish the bioactivation of hydroxydihydropteroate to hydroxydihydrofolate. Introduction of a wild-type copy of folC fully restores PAS susceptibility in folC mutant strains Mycobacterium tuberculosis variant bovis
malfunction in Mycobacterium tuberculosis clinical isolates missense mutations within the coding sequence of the folC gene cause alterations within the 7,8-dihydropteroate binding pocket resulting in 4-aminosalicylic acid resistance. The alterations in the substrate binding pocket result in reduced dihydrofolate synthase activity and abolish the bioactivation of hydroxydihydropteroate to hydroxydihydrofolate. Introduction of a wild-type copy of folC fully restores PAS susceptibility in folC mutant strains Mycobacterium tuberculosis