Electrical stimulation of serotonergic neurons in the raphe nuclei of the midbrain or medulla enhances the formation of serotonin in vivo in the terminal projections of these neurons [I]. The acceleration of serotonin synthesis results from an increase in the conversion of tryptophan to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase [2,3] [EC 1.14.16.4 tryptophan-5-monooxygenase: L-trypt...

The role of serotonin (5-HT) in psychopathology has been investigated for decades. Among others, symptoms of depression, panic, aggression and suicidality have been associated with serotonergic dysfunction. Here we summarize the evidence that low brain 5-HT signals a metabolic imbalance that is evolutionarily conserved and not specific for any specific psychiatric diagnosis. The synthesis and n...

Mixed dissociation constants of four drug acids, i.e. silychristin, silybinin, silydianin and mycophenolate at various ionic strengths I of range 0.01 and 0.30 and at temperatures of 25 and 37 ◦C were determined using the SQUAD(84) regression analysis program applied to pH-spectrophotometric titration data. The proposed strategy of an efficient experimentation in a protonation constants determi...

Prodiginine molecules (prodigiosin and obatoclax) are well-known pH-chromic dyes with promising anti-tumor properties. They present multiple tautomeric and rotameric forms. The protonation state and the structure of such flexible ligands in interaction with a protein are crucial to understand and to model the protein's biological activities. The determination of the protonation state via UV/vis...

In protein-ligand binding, the electrostatic environments of the two binding partners may vary significantly in bound and unbound states, which may lead to protonation changes upon binding. In cases where ligand binding results in a net uptake or release of protons, the free energy of binding is pH-dependent. Nevertheless, conventional free energy calculations and molecular docking protocols ty...

The interaction of the trp repressor from Escherichia coli with a 20 bp fragment of DNA (CGTACTGATT.AATCAGTACG) corresponding to a mutant trp operator was studied by c.d. in the presence and absence of the co-repressor, L-tryptophan, and as a function of the concentration of K+ and Na+ ions. The affinity of the repressor for the mutant operator in the presence of tryptophan is about three order...

The protonation of the ligand molecule and the protein binding site has a significant influence on the results obtained by protein-ligand docking. Due to the inability of X-ray crystallography to resolve the hydrogen atom in protein and protein complex structures, the correct protonation for the protein and the ligand has to be assigned on a theoretical basis before the structures can be used. ...