A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by a de novo crystal structural and spectroscopic study

Abstract

SfmD is a heme-dependent enzyme in the biosynthetic pathway of saframycin A. Here, we present a 1.78-Å resolution de novo crystal structure of SfmD, which unveils a novel heme cofactor...

Molecular Rationale for Partitioning between C–H and C–F Bond Activation in Heme-Dependent Tyrosine Hydroxylase

“…TDO belongs to a histidine-ligated heme dioxygenase superfamily, oxidizing tryptophan or tryptophan-derived substrates with a ferrous heme and molecular oxygen. Indoleamine 2,3-dioxygenase (IDO), PrnB, and MarE are also members of this enzyme family, and the former two have been structurally characterized. − Recently, SfmD as a 3-methyl- l -tyrosine hydroxylase involved in the biosynthesis of saframycin has been identified and structurally resembles the TDO superfamily enzymes . Despite the conservation of the global tertiary fold, the overall rmsd values upon superposition of the structures are strikingly poor due to diverse structural topology.…”

“…Surprisingly, even though TyrH and SfmD catalyze the same Tyr-based, ortho -hydroxylation, they have distinct heme cofactors, binding domains, and relative positions (Figure S14). These enzymes may be related in an evolutionary perspective, considering TyrH and SfmD both exhibit slow oxygen-dependent hydroxylation activities in the presence of ascorbate, , while the TDO superfamily members can exhibit monooxygenation reactivity. , We expect to explore more biochemical implications of these related enzymes in the near future and thus, better understand the evolution and structure–function relationships among these histidine-ligated heme enzymes catalyzing aromatic amino acid oxygenation reactions.…”

“…56−58 Recently, SfmD as a 3-methyl-L-tyrosine hydroxylase involved in the biosynthesis of saframycin has been identified and structurally resembles the TDO superfamily enzymes. 59 Despite the conservation of the global tertiary fold, the overall rmsd values upon superposition of the structures are strikingly poor due to diverse structural topology. Hence, the deficiency of structural homology observed among these enzymes precludes the possibility of using molecular replacement methods to solve the structure of TyrH or vice versa.…”

Promoting CO2 Electroreduction Kinetics on Atomically Dispersed Monovalent ZnI Sites by Rationally Engineering Proton‐Feeding Centers

“…Recently,a tomically-dispersed non-precious metal-N 4 (M-N 4 )m oieties anchored on pyrolyzed carbon (M-N 4 /C) catalysts have attracted much attention, [7] which show as ignificant impact on promoting the intrinsic CO 2 RR performance by facilitating the charge transfer from M-N x moieties to CO 2 molecular and then activating adsorbed CO 2 species. [8] Despite the most promising CO 2 RR activity obtained with M-N 4 /C catalysts,t heir catalytic performance still needs to be further improved for practical applications.C ompared to biological systems of heme-based enzymes (M-N 4 configuration), [9] it can be found that most of the currently reported M-N 4 /C catalysts are plane symmetrical structure, similar with phthalocyanine [10] or porphyrin structure. [11] Nevertheless,the plane symmetrical structure of the M-N 4 moieties usually faces ah ighreaction free energy for the water dissociation step,o wing to their sluggish proton-feeding kinetics in coupling with protons and electrons for CO production [Eqs.…”

Promoting CO2 Electroreduction Kinetics on Atomically Dispersed Monovalent ZnI Sites by Rationally Engineering Proton‐Feeding Centers

“…Recently,a tomically-dispersed non-precious metal-N 4 (M-N 4 )m oieties anchored on pyrolyzed carbon (M-N 4 /C) catalysts have attracted much attention, [7] which show as ignificant impact on promoting the intrinsic CO 2 RR performance by facilitating the charge transfer from M-N x moieties to CO 2 molecular and then activating adsorbed CO 2 species. [8] Despite the most promising CO 2 RR activity obtained with M-N 4 /C catalysts,t heir catalytic performance still needs to be further improved for practical applications.C ompared to biological systems of heme-based enzymes (M-N 4 configuration), [9] it can be found that most of the currently reported M-N 4 /C catalysts are plane symmetrical structure, similar with phthalocyanine [10] or porphyrin structure. [11] Nevertheless,the plane symmetrical structure of the M-N 4 moieties usually faces ah ighreaction free energy for the water dissociation step,o wing to their sluggish proton-feeding kinetics in coupling with protons and electrons for CO production [Eqs.…”