001) PT, although still in the normal range, was prolonged in pa

001). PT, although still in the normal range, was prolonged in patients with hyperprolactinemia as compared to the control group (13.53 +/- 1.39 vs. 12.65 +/- 0.53 s; p=0.03) and normalized after therapy (12.69 +/- 0.65 vs. 12.65 +/- 0.53 s; p=0.88). TT, although in normal range, was significantly shorter in the hypeprolactinemic patients than in the controls (14.34 +/- 4.52 vs. 17.21 +/- 1.35 s; p smaller than 0.025) and after treatment remained significantly shorter than in the controls (15.17

+/- 1.55 vs. 17.21 +/- 1.35 s; p smaller than 0.0001). D-dimer values before treatment in the patients with hyperproplactinemia were above the normal range (239.47 +/- 107.93 vs. 131.27 +/- 50.64 ng/ml, p=0.002) and decreased to normal values after therapy (239.47 +/- 107.93 vs. 146.60 +/- 39.15 ng/ml; p smaller than 0.001). D-dimer levels correlated with PRL (r=0.30) and the change in serum D-dimer values significantly correlated with the change in PRL levels during therapy GSI-IX (r=0.62). aPTT, vWFAg and SN-38 order fibrinogen were similar in patients and controls. Conclusion In our study, increased thrombin generation that resulted in elevated D-dimer levels may be one of the contributing factors to the prethrombotic state in patients with hyperprolactinemia.”
“Correlated networks of amino acids have been proposed to play a fundamental role in allostery and enzyme catalysis. These networks of amino

acids can be traced from surface-exposed residues all the way into the active site, and disruption of these JQ-EZ-05 networks can decrease enzyme activity. Substitution of the distal Gly121 residue in Escherichia coil dihydrofolate reductase results in an up to 200-fold decrease in the hydride transfer rate despite the fact that the residue is located 15 angstrom from the active-site center. In this study, nuclear magnetic resonance relaxation experiments are used to demonstrate that dynamics on the picosecond to nanosecond and microsecond to millisecond time scales are changed significantly in the G121V mutant of dihydrofolate reductase. In particular, picosecond to nanosecond time scale dynamics are decreased in the FG loop (containing the mutated residue at position

121) and the neighboring active-site loop (the Met20 loop) in the mutant compared to those of the wild-type enzyme, suggesting that these loops are dynamically coupled. Changes in methyl order parameters reveal a pathway by which dynamic perturbations can be propagated more than 25 angstrom across the protein from the site of mutation. All of the enzyme complexes, including the model Michaelis complex with folate and nicotinamide adenine dinudeotide phosphate bound, assume an occluded ground-state conformation, and we do not observe sampling of a higher-energy closed conformation by N-15 R-2 relaxation dispersion experiments. This is highly significant, because it is only in the closed conformation that the cofactor and substrate reactive centers are positioned for reaction.

Comments are closed.