15 research outputs found
Ivabradine use in pregnant women—treatment indications and pregnancy outcome: an evaluation of the German Embryotox database
Determination of both the time constant of vO2 and DeltavO2/DeltaW from a single incremental exercise test: validation and repeatability
Polyglycine Acts as a Rejection Signal for Protein Transport at the Chloroplast Envelope
The Reduced Plastid-Encoded Polymerase-Dependent Plastid Gene Expression Leads to the Delayed Greening of the Arabidopsis fln2 Mutant
Protein motions, dynamic effects and thermal stability in dihydrofolate reductase from the hyperthermophile thermotoga maritima
Dihydrofolate reductase (DHFR) has long been used as a model system in studies of the relationship between enzyme structure and catalysis. DHFR from the hyperthermophilic bacterium Thermotoga maritima (TmDHFR) is substantially different to other chromosomal DHFRs. It is dimeric where most others are monomeric, it lacks the conformational behaviour of monomeric DHFRs, and the kinetics of the catalysed reaction are significantly different. Experimental and computational studies of TmDHFR and comparison to other DHFRs have yielded deep insights into the role of enzyme motions and dynamics in catalysis. Mutational studies and formation of hybrids between TmDHFR and a monomeric homologue have demonstrated that dimerisation is required for extreme thermostability, but also leads to an inability to adequately close the active site with detrimental effects for the speed of the catalysed reaction. However, in common with other DHFRs there is no involvement of large-scale enzyme motions in the chemical reaction itself and dynamic coupling to the reaction coordinate is efficiently minimised. Studies of DHFRs from hyperthermophilic organisms and comparisons to their mesophilic counterparts remain a rich source of information on the fundamental nature of enzyme catalysis