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.

Heterometallic [AgFe(3)S (4)] ferredoxin variants: synthesis, characterization, and the first crystal structure of an engineered heterometallic iron-sulfur protein.

Heterometallic [AgFe(3)S(4)] iron-sulfur clusters assembled in wild-type Pyrococcus furiosus ferredoxin and two variants, D14C and D14H, are characterized. The crystal structure of the [AgFe(3)S(4)] D14C variant shows that the silver(I) ion is indeed part of the cluster and is coordinated to the thiolate group of residue 14. Cyclic voltammetry shows one redox pair with a reduction potential of +220 mV versus the standard hydrogen electrode which is assigned to the [AgFe(3)S(4)](2+/+) couple.

Experimentally calibrated computational chemistry of tryptophan hydroxylase: trans influence, hydrogen-bonding, and 18-electron rule govern O2-activation.

Insight into the nature of oxygen activation in tryptophan hydroxylase has been obtained from density functional computations. Conformations of O(2)-bound intermediates have been studied with oxygen trans to glutamate and histidine, respectively. An O(2)-adduct with O(2)trans to histidine (O(his)) and a peroxo intermediate with peroxide trans to glutamate (P(glu)) were found to be consistent (0.