Thiol dioxygenases are mononuclear non-heme Fe-dependent metalloenzymes that initiate the oxidative catabolism of thiol-containing substrates to their respective sulfinates. Cysteine dioxygenase (CDO), the best characterized mammalian thiol dioxygenase, contains a three-histidine (3-His) coordination environment rather than the 2-His-1-carboxylate facial triad seen in most mononuclear non-heme Fe enzymes. A similar 3-His active site is found in the bacterial thiol dioxygenase 3-mercaptopropionate dioxygenase (MDO), which converts 3-mercaptopropionate into 3-sulfinopropionic acid as part of the bacterial sulfur metabolism pathway. In this study, we have investigated the active site geometric and electronic structures of a third non-heme Fe-dependent thiol dioxygenase, cysteamine dioxygenase (ADO), by using a spectroscopic approach. Although a 3-His facial triad had previously been implicated on the basis of sequence alignment and site-directed mutagenesis studies, little is currently known about the active site environment of ADO. Our magnetic circular dichroism and electron paramagnetic resonance data provide compelling evidence that ADO features a 3-His facial triad, like CDO and MDO. Despite this similar coordination environment, spectroscopic results obtained for ADO incubated with various substrate analogues are distinct from those obtained for the other Fe-dependent thiol dioxygenases. This finding suggests that the secondary coordination sphere of ADO is distinct from those of CDO and MDO, demonstrating the significant role that secondary-sphere residues play in dictating substrate specificity.
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http://dx.doi.org/10.1021/acs.biochem.0c00267 | DOI Listing |
J Inorg Biochem
March 2025
Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States. Electronic address:
The synthesis and characterization of a new ligand, 1-(bis(pyridin-2-ylmethyl) amino)-2-methylpropane-2-thiolate (BPAS) and its nonheme iron complex, Fe(BPAS)Br (1), is reported. Reaction of 1 with O at -20 °C generates a high-spin iron(III)-hydroxide complex, [Fe(OH)(BPAS)(Br)] (2), that was characterized by UV-vis, Fe Mössbauer, and electron paramagnetic resonance (EPR) spectroscopies, and electrospray ionization mass spectrometry (ESI-MS). Density functional theory (DFT) calculations were employed to support the spectroscopic assignments.
View Article and Find Full Text PDFJ Anim Sci
January 2024
Department of Animal Sciences, Auburn University, Auburn, AL 36849, USA.
Weaning stress in pigs is associated with low feed intake and poor nutrient utilization. Cysteine is a sulfur amino acid with key roles in pig production, but how cysteine metabolism and requirements are affected by weaning stress should be better defined. The objective of this study was to determine the collective impact of weaning and feed restriction on tissue cysteine metabolism.
View Article and Find Full Text PDFBiochim Biophys Acta Proteins Proteom
January 2025
Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, United States. Electronic address:
Oxidation and assimilation of persulfides in bacteria is often catalyzed by a persulfide dioxygenase and sulfurtransferase in consecutive reactions. Enzymes responsible for the oxidation of persulfides have not been clearly defined in Pseudomonas aeruginosa PAO1. The characterized mercaptopropionate dioxygenase (MDO) in P.
View Article and Find Full Text PDFNeuroprotection
September 2024
Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany.
Sci Adv
October 2024
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
2-Aminoethanethiol dioxygenase (ADO) is a thiol dioxygenase that sulfinylates cysteamine and amino-terminal cysteines in polypeptides. The pathophysiological roles of ADO remain largely unknown. Here, we demonstrate that ADO expression represents a vulnerability in cancer cells, as ADO depletion led to loss of proliferative capacity and survival in cancer cells and reduced xenograft growth.
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