The nature of the proton transfer from an acid group at the active site of an enzyme, to solvent water. The extent of 2H and 3H transfer in the reaction catalysed by triose phosphate isomerase

1975 ◽  
Vol 10 ◽  
pp. 154 ◽  
Author(s):  
L. Mark Fisher ◽  
W. John Albery ◽  
Jeremy R. Knowles
Keyword(s):  
Proton Transfer ◽  
Active Site ◽  
Acid Group ◽  
Triose Phosphate Isomerase ◽  
Triose Phosphate ◽  
Solvent Water

Uniquely Labelled Active Site Sequence in Chicken Muscle Triose Phosphate Isomerase

Nature ◽  
1970 ◽  
Vol 227 (5254) ◽  
pp. 180-181 ◽  
Author(s):  
A. F. W. COULSON ◽  
J. R. KNOWLES ◽  
J. D. PRIDDLE ◽  
R. E. OFFORD
Keyword(s):  
Active Site ◽  
Triose Phosphate Isomerase ◽  
Triose Phosphate ◽  
Chicken Muscle ◽  
Active Site Sequence

Chemistry of proton abstraction by glycolytic enzymes (aldolase, isomerases and pyruvate kinase)

1981 ◽  
Vol 293 (1063) ◽  
pp. 131-143 ◽  
Keyword(s):  
Proton Transfer ◽  
Pyruvate Kinase ◽  
Triose Phosphate Isomerase ◽  
Transfer Mechanism ◽  
Glycolytic Enzymes ◽  
Structural Homology ◽  
Large Measure ◽  
Proton Abstraction ◽  
Triose Phosphate

Intermediates have been synthesized that are rapidly utilized by triose phosphate isomerase, yeast aldolase and pyruvate kinase. In each case the compounds have the properties of an enol expected for a stepwise proton transfer mechanism. Apparently the apparatus required for doing this chemistry is sufficiently unique for a large measure of structural homology to have been imposed upon the enzymes of this class during evolution.

scholarly journals Molecular dynamics simulations of the interactions between triose phosphate isomerase and sulfonamides

2020 ◽  
Vol 2 ◽  
pp. e13
Author(s):  
Neville Y. Forlemu ◽  
Joseph Sloop
Keyword(s):  
Active Site ◽  
Malaria Incidence ◽  
Antimalarial Drugs ◽  
Glycolytic Enzyme ◽  
Triose Phosphate Isomerase ◽  
Van Der Waals Interactions ◽  
Dimer Interface ◽  
Triose Phosphate ◽  
Solvation Energies ◽  
Active Site Region

Malaria is a disease with debilitating health and negative economic impacts in regions at high risk of infection. Parasitic resistance and side effects of current antimalarial drugs are major setbacks to the successful campaigns that have reduced malaria incidence by 40% in the last decade. The parasite’s dependence on glycolysis for energy requirements makes pathway enzymes suitable targets for drug development. Specifically, triose phosphate isomerase (TPI) from Plasmodium falciparum (pTPI) and human (hTPI) cells show striking structural features that can be used in development of new antimalarial agents. In this study MD simulations were used to characterize binding sites on hTPI and pTPI interactions with sulfonamides. The molecular mechanics Poisson–Boltzmann surface area (MM–PBSA) method was used to estimate the interaction energies of four sulfonamide-TPI docked complexes. A unique combination of key residues at the dimer interface of pTPI is responsible for the observed selective affinity to pTPI compared to hTPI. The representative sulfonamide; 4-amino-N-(3,5-dimethylphenyl)-3-fluorbenzenesulfonamide (sulfaE) shows a strong affinity with pTPI (dimer interface, −42.91 kJ/mol and active site region, −71.62 kJ/mol), hTPI (dimer interface, −41.32 kJ/mol and active site region, −84.40 kJ/mol). Strong and favorable Van der Waals interactions and increases in non-polar solvation energies explain the difference in affinity between pTPI with sulfaE compared to hTPI at the dimer interface. This is an indication that the dimer interface of TPI glycolytic enzyme is vital for development of sulfonamide based antimalarial drugs.

Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate

Biochemistry ◽  
1986 ◽  
Vol 25 (22) ◽  
pp. 7142-7154 ◽  
Author(s):  
Ronald T. Raines ◽  
Eliza L. Sutton ◽  
Donald R. Straus ◽  
Walter Gilbert ◽  
Jeremy R. Knowles
Keyword(s):  
Active Site ◽  
Triose Phosphate Isomerase ◽  
Triose Phosphate
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