Amino Acid Oxidation: A Combined Study of Cysteine Oxo Forms by IRMPD Spectroscopy and Simulations

Abstract

The redox activity of cysteine sulfur allows numerous post-translational protein modifications involved in the oxidative regulation of metabolism, in metal binding, and in signal transduction. A combined approach based on infrared multiple photon dissociation spectroscopy at the Centre Laser Infrarouge d'Orsay (CLIO) free electron laser facility, calculations of IR frequencies, and finite temperature ab initio molecular dynamics simulations has been employed to characterize the gas-phase structures of deprotonated cysteine sulfenic, sulfinic, and sulfonic acids, [cysSO ] (x=1, 2, 3, representing the number of S-bound oxygen atoms), which are key intermediates in the redox-switching chemistry of proteins. The ions show different structural motifs owing to preferential binding of the proton to either the carboxylate or sulfur-containing group. Due to the decreasing basicity of the sulfenic, sulfinic, and sulfonic terminals, the proton bound to SO in [cysSO] migrates to the carboxylate in [cysSO ] , whereas it turns out to be shared in [cysSO ] . Evidence is gathered that a mixture of close-lying low-energy conformers is sampled for each cysteine oxo form in a Paul ion trap at room temperature.

Vibrational spectroscopy of deprotonated peptides containing an acidic side chain

“…[Cys-H]has been further characterized by low temperature IRPD [16], showing that non-classical proton sharing is likely to occur at least in cryogenic conditions. A similar trend was noted [17] for [CysSO 2 -H]with a shared-proton, as opposed to [CysSO-H]and [CysSO 3 -H]for which it is localized either on the oxidized side chain or on the carboxylate. This non-classical behavior prompted us to undertake IRMPD measurements on deprotonated Asp [12] and Glu, and on a series of deprotonated carboxylic diacids [18].…”

“…To make the picture even more complex, species in which a proton is shared by chemically different sites may [16,17] or may not [17,27,28] lead to IR signatures of unusual proton sharing at room temperature, similar to those described above for GD and GGD. Deprotonated cysteines with different oxidization states were shown to switch from hydrogen-bound oxidized side chain in [CysSO-H]to a shared-proton in [CysSO 2 -H]to a hydrogen-bound carboxylate in [CysSO 3 -H] - [17], underlining the importance of the relative proton affinities of the two anions. Still, nearly degenerate cases do not all generate unusual vibrational features [27,28].…”

l-Cysteine Modified by S-Sulfation: Consequence on Fragmentation Processes Elucidated by Tandem Mass Spectrometry and Chemical Dynamics Simulations

“…This method was used since it is able to provide good geometries and vibrational frequencies as reported in Ref. 8. In the case of a TS, an intrinsic reaction coordinate (IRC) calculation was performed to verify that it correctly connects the two minima.…”

“…In a previous contribution, some of us have applied low-energy collision-induced dissociation (CID) 7 mass spectrometry to deprotonated L-cysteine S-sulfate, formed by electrospray ionization, [cysS-SO 3 ] -, to generate and interrogate the cysteine sulfenic intermediate, [cysSO] -, by vibrational spectroscopy and ab initio molecular dynamics simulations. 8 The transient nature of cysteine sulfenate [cysSO]makes its isolation and characterization highly demanding in the condensed phase. 9 The reported unimolecular rearrangement is reminiscent of the CID behavior of aromatic sulfonate ions which yield phenoxide ions upon the loss of SO 2 .…”

Complexation of halide ions to tyrosine: role of non-covalent interactions evidenced by IRMPD spectroscopy

“…3 In addition, other non-covalent contacts, including anion-π effects favored between π-acidic arenes and charge-diffuse anions, may contribute in stabilizing negatively charged adducts of (aromatic) amino acids. Recently, Infrared Multiple Photon Dissociation (IRMPD) spectroscopy, [4][5][6][7] a powerful tool to identify the structural and electronic features of various ionic species in the gas phase, [8][9][10][11][12][13][14] including mono- [15][16] and divalent- 17 metal-bound amino acids, has revealed canonical structures for halide adducts of glutamic acid, histidine, and phenylalanine. 18 In contrast arginine is rather in the zwitterionic form 19 , and canonical and zwitterionic isomers are both significantly populated in the proline-chloride complex.…”