Elucidating the interaction of H 2 O 2 with polar amino acids – Quantum chemical calculations

Karmakar, Tarak; Balasubramanian, Sundaram

doi:10.1016/j.cplett.2014.08.041

Cited by 3 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rationalization for their behavior begins with an interaction of H 2 O 2 via hydrogen bonding with histidine, arginine, as well as with tyrosine, cysteine, threonine, glutamine, aspartic acid, lysine, methionine, tyrosine, and tryptophan. 53 This interaction gives rise to a high local concentration of H 2 O 2 at the protein in the vicinity of these amino-acid residues, allowing photolysis to produce a high local concentration of • OH where the first • OH adds onto histidine and abstracts the • H from arginine, and another • OH, in close proximity, reacts with the radical intermediate. Such reaction pathways contrast significantly with synchrotronbased HRF, 13,50 where no local fluctuation of • OH concentration is expected because the radical precursor is a water molecule.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Although both synchrotron-based HRF and FPOP utilize • OH as labeling reagents, they are likely to be mechanistically different. In FPOP, • OH is from photolysis of H 2 O 2 , whose distribution in a protein solution is potentially heterogeneous due to localized hydrogen bonding between selected amino acid residues and H 2 O 2 . The heterogeneity of an H 2 O 2 distribution prior to laser irradiation will induce fluctuations in local • OH concentration during labeling and possibly alter the oxygen-uptake scheme for selected residues and can be potentially utilized to tailor the labeling conditions.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by ¹⁸O Isotopic Labeling

Liu

Zhang

et al. 2019

Anal. Chem.

View full text Add to dashboard Cite

Fast photochemical oxidation of protein (FPOP) has become an important mass spectrometrybased protein footprinting approach. Although the hydroxyl radical (•OH) generated by photolysis of hydrogen peroxide (H 2 O 2 ) is most commonly used, the pathways for its reaction with aminoacid side chains remain unclear. Here we report a systematic study of •OH oxidative modification of 13 amino acid residues by using 18 O isotopic labeling. The results differentiate three classes of residues on the basis of their oxygen uptake preference towards different oxygen sources. Histidine, arginine, tyrosine and phenylalanine residues preferentially take oxygen from H 2 O 2 . Methionine residues competitively take oxygen from H 2 O 2 and dissolved oxygen (O 2 ) whereas the remaining residues take oxygen exclusively from O 2 . Results reported in this work deepen the understanding of •OH labeling pathway on a FPOP platform, opening new possibilities for tailoring FPOP conditions in addressing many biological questions in a profound way.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by ¹⁸O Isotopic Labeling

Liu

Zhang

et al. 2019

Anal. Chem.

View full text Add to dashboard Cite

show abstract

“…A recent quantum calculation study revealed the hydrogen bonding between H 2 O 2 and amino acids including His, Arg, Tyr, Cys, Thr, Gln, Asp, Lys, Met, and Trp. 936 Such hydrogen bonding will induce a preformed H 2 O 2 −amino acid residue complex, which will result in a local fluctuation in • OH concentrations upon laser photolysis. Liu, Gross, and co-workers 145 studied the reaction pathways between • OH and 13 different amino acid residues on a FPOP platform.…”

Section: γ-Ray-basedmentioning

confidence: 99%

“…In contrast to the two systems mentioned above, where uniformly distributed water is the • OH precursor, any H 2 O 2 photolysis approach, as represented by FPOP, follows slightly different reaction pathways. A recent quantum calculation study revealed the hydrogen bonding between H 2 O 2 and amino acids including His, Arg, Tyr, Cys, Thr, Gln, Asp, Lys, Met, and Trp . Such hydrogen bonding will induce a preformed H 2 O 2 –amino acid residue complex, which will result in a local fluctuation in • OH concentrations upon laser photolysis.…”

Section: Fast Labeling Reagents: Reactive Radical Speciesmentioning

confidence: 99%

Mass Spectrometry-Based Protein Footprinting for Higher-Order Structure Analysis: Fundamentals and Applications

2020

View full text Add to dashboard Cite

Proteins adopt different higher-order structures (HOS) to enable their unique biological functions. Understanding the complexities of protein higher-order structures and dynamics requires integrated approaches, where mass spectrometry (MS) is now positioned to play a key role. One of those approaches is protein footprinting. Although the initial demonstration of footprinting was for the HOS determination of protein/nucleic acid binding, the concept was later adapted to MS-based protein HOS analysis, through which different covalent labeling approaches “mark” the solvent accessible surface area (SASA) of proteins to reflect protein HOS. Hydrogen–deuterium exchange (HDX), where deuterium in D2O replaces hydrogen of the backbone amides, is the most common example of footprinting. Its advantage is that the footprint reflects SASA and hydrogen bonding, whereas one drawback is the labeling is reversible. Another example of footprinting is slow irreversible labeling of functional groups on amino acid side chains by targeted reagents with high specificity, probing structural changes at selected sites. A third footprinting approach is by reactions with fast, irreversible labeling species that are highly reactive and footprint broadly several amino acid residue side chains on the time scale of submilliseconds. All of these covalent labeling approaches combine to constitute a problem-solving toolbox that enables mass spectrometry as a valuable tool for HOS elucidation. As there has been a growing need for MS-based protein footprinting in both academia and industry owing to its high throughput capability, prompt availability, and high spatial resolution, we present a summary of the history, descriptions, principles, mechanisms, and applications of these covalent labeling approaches. Moreover, their applications are highlighted according to the biological questions they can answer. This review is intended as a tutorial for MS-based protein HOS elucidation and as a reference for investigators seeking a MS-based tool to address structural questions in protein science.

show abstract

“…F29, F35, and F55 are all within ∼10 Å of the mutation site, hence hydroxyl radical attack on nearby, less reactive/less solvent exposed groups in the region could be expected to be more likely in STT. Recent reports have suggested that hydrogen peroxide preferentially interacts with certain side-chains, including threonine, but not leucine residues. , As such, an alternative explanation for the increased modification on F55 in STT, is that the L57T mutation increases the local concentration of hydrogen peroxide. Although the effects of local microenvironment in FPOP have not been fully explored, the local microenvironment changes discussed here provide an alternative explanation as the cause of the changes in oxidation observed in this region.…”

Section: Resultsmentioning

confidence: 99%

Long-Range Conformational Changes in Monoclonal Antibodies Revealed Using FPOP-LC-MS/MS

et al. 2019

View full text Add to dashboard Cite

Differences in conformational dynamics between two full-length monoclonal antibodies have been probed in detail using Fast Photochemical Oxidation of Proteins (FPOP) followed by proteolysis and LC-ESI-MS/MS analyses. FPOP uses hydroxyl radical labeling to probe the surface-accessible regions of proteins and has the advantage that the resulting covalent modifications are irreversible, thus permitting optimal downstream analysis. Despite the two monoclonal antibodies (mAbs) differing by only three amino acids in the heavy chain complementarity determining regions (CDRs), one mAb, MEDI1912-WFL, has been shown to undergo reversible self-association at high concentrations and exhibited poor pharmacokinetic properties in vivo, properties which are markedly improved in the variant, MEDI1912-STT. Identifying the differences in oxidative labeling between the two antibodies at residue level revealed long-range effects which provide a key insight into their conformational differences. Specifically, the amino acid mutations in the CDR region of the heavy chain resulted in significantly different labeling patterns at the interfaces of the CL–CH1 and CH1–CH2 domains, with the nonaggregating variant undergoing up to four times more labeling in this region than the aggregation prone variant, thus suggesting a change in the structure and orientation of the CL–CH1 interface. The wealth of FPOP and LC-MS data obtained enabled the study of the LC elution properties of FPOP-oxidized peptides. Some oxidized amino acids, specifically histidine and lysine, were noted to have unique effects on the retention time of the peptide, offering the promise of using such an analysis as an aid to MS/MS in assigning oxidation sites.

show abstract

Elucidating the interaction of H 2 O 2 with polar amino acids – Quantum chemical calculations

Cited by 3 publications

References 50 publications

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by ¹⁸O Isotopic Labeling

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by ¹⁸O Isotopic Labeling

Mass Spectrometry-Based Protein Footprinting for Higher-Order Structure Analysis: Fundamentals and Applications

Long-Range Conformational Changes in Monoclonal Antibodies Revealed Using FPOP-LC-MS/MS

Contact Info

Product

Resources

About

Elucidating the interaction of H 2 O 2 with polar amino acids – Quantum chemical calculations

Cited by 3 publications

References 50 publications

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by 18O Isotopic Labeling

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by 18O Isotopic Labeling

Mass Spectrometry-Based Protein Footprinting for Higher-Order Structure Analysis: Fundamentals and Applications

Long-Range Conformational Changes in Monoclonal Antibodies Revealed Using FPOP-LC-MS/MS

Contact Info

Product

Resources

About

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by ¹⁸O Isotopic Labeling

Hydroxyl-Radical Reaction Pathways for the Fast Photochemical Oxidation of Proteins Platform As Revealed by ¹⁸O Isotopic Labeling