Substrate and pH-Dependent Kinetic Profile of 3-Mercaptopropionate Dioxygenase from Pseudomonas aeruginosa

Biochemistry
Matthias FellnerGuy N L Jameson

Abstract

Thiol dioxygenases catalyze the synthesis of sulfinic acids in a range of organisms from bacteria to mammals. A thiol dioxygenase from the bacterium Pseudomonas aeruginosa oxidizes both 3-mercaptopropionic acid and cysteine, with a ∼70 fold preference for 3-mercaptopropionic acid over all pHs. This substrate reactivity is widened compared to other thiol dioxygenases and was exploited in this investigation of the residues important for activity. A simple model incorporating two protonation events was used to fit profiles of the Michaelis-Menten parameters determined at different pH values for both substrates. The pKs determined using plots of k(cat)/Km differ at low pH, but not in a way easily attributable to protonation of the substrate alone and share a common value at higher pH. Plots of k(cat) versus pH are also quite different at low pH showing the monoprotonated ES complexes with 3-mercaptopropionic acid and cysteine have different pKs. At higher pH, k(cat) decreases sigmoidally with a similar pK regardless of substrate. Loss of reactivity at high pH is attributed to deprotonation of tyrosine 159 and its influence on dioxygen binding. A mechanism is proposed by which deprotonation of tyrosine 159 both blocks oxygen binding...Continue Reading

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Citations

May 20, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Matthias FellnerGuy N L Jameson
Jun 9, 2020·Chemical Society Reviews·Yifan Wang, Aimin Liu
Jun 27, 2018·Nature Chemical Biology·Jiasong LiAimin Liu
May 3, 2019·Biochemistry·Sekotilani AloiGuy N L Jameson
Jun 13, 2017·Journal of the American Chemical Society·Abayomi S FaponleSam P de Visser
Jul 27, 2021·Chemistry : a European Journal·C-C George YehSam P de Visser

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