Spectroscopic and Computational Insights into the Mechanism of Cofactor Cobalt-Carbon Bond Homolysis by the Adenosylcobalamin-Dependent Enzyme Ethanolamine Ammonia-Lyase.

The adenosylcobalamin (AdoCbl)-dependent enzyme ethanolamine ammonia-lyase (EAL) catalyzes the conversion of ethanolamine to acetaldehyde and ammonia. As is the case for all AdoCbl-dependent isomerases, the catalytic cycle of EAL is initiated by homolytic cleavage of the cofactor's Co-C bond, producing Cocobalamin (CoCbl) and an adenosyl radical that serves to abstract a hydrogen atom from the substrate. Remarkably, in the presence of substrate, the rate of Co-C bond homolysis of enzyme-bound AdoCbl is increased by 12 orders of magnitude.

Vibronic Coupling in Vitamin B: A Combined Spectroscopic and Computational Study.

Understanding the diverse reactivities of vitamin B and its derivatives, collectively called cobalamins, requires detailed knowledge of their geometric and electronic structures. Electronic absorption (Abs) and resonance Raman (rR) spectroscopies have proven invaluable in this area, particularly when used in concert with computational techniques such as density functional theory (DFT). There remain, however, lingering uncertainties in the computational description of electronic excited states of cobalamins, particularly surrounding the vibronic coupling that impacts the Abs bandshapes and gives rise to rR enhancement of vibrational modes.

Electronic structure studies of free and enzyme-bound B species by magnetic circular dichroism and complementary spectroscopic techniques.

Electronic absorption (Abs) and circular dichroism (CD) spectroscopic techniques have been used successfully for over half a century in studies of free and enzyme-bound B species. More recently, magnetic circular dichroism (MCD) spectroscopy and other complementary techniques have provided an increasingly detailed understanding of the electronic structure of cobalamins. While CD spectroscopy measures the difference in the absorption of left- and right-circularly polarized light, MCD spectroscopy adds the application of a magnetic field parallel to the direction of light propagation.

The Crystal Structure of Cysteamine Dioxygenase Reveals the Origin of the Large Substrate Scope of This Vital Mammalian Enzyme.

We report the crystal structure of the mammalian non-heme iron enzyme cysteamine dioxygenase (ADO) at 1.9 Å resolution, which shows an Fe and three-histidine (3-His) active site situated at the end of a wide substrate access channel. The open approach to the active site is consistent with the recent discovery that ADO catalyzes not only the conversion of cysteamine to hypotaurine but also the oxidation of N-terminal cysteine (Nt-Cys) peptides to their corresponding sulfinic acids as part of the eukaryotic N-degron pathway.