D-3-Phosphoglycerate Dehydrogenase from Mycobacterium tuberculosis Is a Link between the Escherichia coli and Mammalian Enzymes | Academic Article individual record
abstract

D-3-Phosphoglycerate dehydrogenase (PGDH) from Mycobacterium tuberculosis has been isolated to homogeneity and displays an unusual relationship to the Escherichia coli and mammalian enzymes. In almost all aspects investigated, the M. tuberculosis enzyme shares the characteristics of the mammalian PGDHs. These include an extended C-terminal motif, substrate inhibition kinetics, dependence of activity levels and stability on ionic strength, and the inability to utilize alpha-ketoglutarate as a substrate. The unique property that the M. tuberculosis enzyme shares with E. coli PGDH that it is very sensitive to inhibition by L-serine, with an I(0.5) = 30 microm. The mammalian enzymes are not inhibited by L-serine. In addition, the cooperativity of serine inhibition appears to be modulated by chloride ion, becoming positively cooperative in its presence. This is modulated by the gain of cooperativity in serine binding for the first two effector sites. The basis for the chloride modulation of cooperativity is not known, but the sensitivity to serine inhibition can be explained in terms of certain amino acid residues in critical areas of the structures. The differential sensitivity to serine inhibition by M. tuberculosis and human PGDH may open up interesting possibilities in the treatment of multidrug-resistant tuberculosis.

author list (cited authors)
Dey, S., Hu, Z., Xu, X. L., Sacchettini, J. C., & Grant, G. A.
publication date
2005
keywords
  • Amino Acid Sequence
  • Models, Genetic
  • Escherichia Coli
  • Drug Resistance, Multiple
  • Protein Binding
  • Potassium Chloride
  • Ions
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Time Factors
  • Cloning, Molecular
  • Dose-Response Relationship, Drug
  • Chlorides
  • Substrate Specificity
  • Liver
  • Kinetics
  • Serine
  • Amino Acid Motifs
  • Binding Sites
  • Mycobacterium Tuberculosis
  • Animals
  • Rats
  • Sequence Homology, Amino Acid
  • Protein Structure, Tertiary
  • Carbohydrate Dehydrogenases
  • Molecular Sequence Data
  • Phosphoglycerate Dehydrogenase
citation count

37