Direct coordination of pterin to Fe enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases.

The pterin-dependent nonheme iron enzymes hydroxylate aromatic amino acids to perform the biosynthesis of neurotransmitters to maintain proper brain function. These enzymes activate oxygen using a pterin cofactor and an aromatic amino acid substrate bound to the Fe active site to form a highly reactive Fe = O species that initiates substrate oxidation. In this study, using tryptophan hydroxylase, we have kinetically generated a pre-Fe = O intermediate and characterized its structure as a Fe-peroxy-pterin species using absorption, Mössbauer, resonance Raman, and nuclear resonance vibrational spectroscopies.

Computing Cellulase Kinetics with a Two-Domain Linear Interaction Energy Approach.

While heterogeneous enzyme reactions play an essential role in both nature and green industries, computational predictions of their catalytic properties remain scarce. Recent experimental work demonstrated the applicability of the Sabatier principle for heterogeneous biocatalysis. This provides a simple relationship between binding strength and the catalytic rate and potentially opens a new way for inexpensive computational determination of kinetic parameters.

Isoform-Specific Substrate Inhibition Mechanism of Human Tryptophan Hydroxylase.

Tryptophan hydroxylase (TPH) catalyzes the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression and irritable bowel syndrome. TPH exists in two isoforms: TPH1 and TPH2. TPH1 catalyzes the initial step in the synthesis of serotonin in the peripheral tissues, while TPH2 catalyzes this step in the brain.

Stabilization of tryptophan hydroxylase 2 by l-phenylalanine-induced dimerization.

Tryptophan hydroxylase 2 (TPH2) catalyses the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression, obsessive compulsive disorder, and schizophrenia. Full-length TPH2 is poorly characterized due to low purification quantities caused by its inherent instability. Three truncated variants of human TPH2 (rc TPH2; regulatory and catalytic domain, NΔ47-rc TPH2; truncation of 47 residues in the N terminus of rc TPH2, and c TPH2; catalytic domain) were expressed, purified, and examined for changes in transition temperature, inactivation rate, and oligomeric state.

Computational investigation of enthalpy-entropy compensation in complexation of glycoconjugated bile salts with β-cyclodextrin and analogs.

The inclusion complexes of glycoconjugated bile salts with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrins (HP-β-CD) in aqueous solution were investigated by molecular dynamics simulations to provide a molecular explanation of the experimentally observed destabilizing effect of the HP substituents. Good agreement with experimental data was found with respect to penetration depths of CDs. An increased degree of HP substitution (DS) resulted in an increased probability of blocking the cavity opening, thereby hindering the bile salt from entering CD.