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Biochimica Et Biophysica Acta Apr 2004In PSII, there are two redox-active tyrosines, D and Z, with different midpoint potentials and different reduction kinetics. The factors responsible for these functional... (Review)
Review
In PSII, there are two redox-active tyrosines, D and Z, with different midpoint potentials and different reduction kinetics. The factors responsible for these functional differences have not yet been elucidated. Recent model compound studies of tyrosinate and of tyrosine-containing dipeptides have demonstrated that perturbations of the amino and amide/imide group occur when the tyrosyl aromatic ring is oxidized [J. Am. Chem. Soc. 124 (2002) 5496]. Accompanying density functional calculations suggested that this perturbation is due to spin density delocalization from the aromatic ring onto the amino nitrogen. The implication of this finding is that spin density delocalization may occur in redox-active, tyrosine-containing enzymes, like Photosystem II. In this paper, we review the supporting evidence for the hypothesis that tyrosyl radical spin density delocalizes into the peptide bond in a conformationally sensitive, sequence-dependent manner. Our experimental measurements on tyrosyl radicals in dipeptides have suggested that the magnitude of the putative spin migration may be sequence-dependent. Vibrational spectroscopic studies on the tyrosyl radicals in Photosystem II, which are consistent with spin migration, are reviewed. Migration of the unpaired spin may provide a mechanism for control of the direction and possibly the rate of electron transfer.
Topics: Electron Spin Resonance Spectroscopy; Electron Transport; Free Radicals; Kinetics; Models, Molecular; Oxidation-Reduction; Photosystem II Protein Complex; Plastoquinone; Spectroscopy, Fourier Transform Infrared; Tyrosine
PubMed: 15100033
DOI: 10.1016/j.bbabio.2003.07.010 -
ELife Jul 2023The activation of Src kinase in cells is strictly controlled by intramolecular inhibitory interactions mediated by SH3 and SH2 domains. They impose structural...
The activation of Src kinase in cells is strictly controlled by intramolecular inhibitory interactions mediated by SH3 and SH2 domains. They impose structural constraints on the kinase domain holding it in a catalytically non-permissive state. The transition between inactive and active conformation is known to be largely regulated by the phosphorylation state of key tyrosines 416 and 527. Here, we identified that phosphorylation of tyrosine 90 reduces binding affinity of the SH3 domain to its interacting partners, opens the Src structure, and renders Src catalytically active. This is accompanied by an increased affinity to the plasma membrane, decreased membrane motility, and slower diffusion from focal adhesions. Phosphorylation of tyrosine 90 controlling SH3-medited intramolecular inhibitory interaction, analogical to tyrosine 527 regulating SH2-C-terminus bond, enables SH3 and SH2 domains to serve as cooperative but independent regulatory elements. This mechanism allows Src to adopt several distinct conformations of varying catalytic activities and interacting properties, enabling it to operate not as a simple switch but as a tunable regulator functioning as a signalling hub in a variety of cellular processes.
Topics: src-Family Kinases; Phosphorylation; src Homology Domains; Tyrosine; Protein-Tyrosine Kinases
PubMed: 37428018
DOI: 10.7554/eLife.82428 -
Chemical Research in Toxicology Apr 2013Soman forms a stable, covalent bond with tyrosine 411 of human albumin, with tyrosines 257 and 593 in human transferrin, and with tyrosine in many other proteins. The...
Soman forms a stable, covalent bond with tyrosine 411 of human albumin, with tyrosines 257 and 593 in human transferrin, and with tyrosine in many other proteins. The pinacolyl group of soman is retained, suggesting that pinacolyl methylphosphonate bound to tyrosine could generate specific antibodies. Tyrosine in the pentapeptide RYGRK was covalently modified with soman simply by adding soman to the peptide. The phosphonylated-peptide was linked to keyhole limpet hemocyanin, and the conjugate was injected into rabbits. The polyclonal antiserum recognized soman-labeled human albumin, soman-mouse albumin, and soman human transferrin but not nonphosphonylated control proteins. The soman-labeled tyrosines in these proteins are surrounded by different amino acid sequences, suggesting that the polyclonal recognizes soman-tyrosine independent of the amino acid sequence. Antiserum obtained after 4 antigen injections over a period of 18 weeks was tested in a competition ELISA where it had an IC50 of 10(-11) M. The limit of detection on Western blots was 0.01 μg (15 picomoles) of soman-labeled albumin. In conclusion, a high-affinity, polyclonal antibody that specifically recognizes soman adducts on tyrosine in a variety of proteins has been produced. Such an antibody could be useful for identifying secondary targets of soman toxicity.
Topics: Animals; Antibodies; Antigens; Enzyme-Linked Immunosorbent Assay; Hemocyanins; Humans; Mice; Oligopeptides; Rabbits; Soman; Tyrosine
PubMed: 23469927
DOI: 10.1021/tx400027n -
Genomics, Proteomics & Bioinformatics Oct 2011Increasing evidence shows that protein phosphorylation on serine, threonine and tyrosine residues is a major regulatory post-translational modification in the bacteria.... (Review)
Review
Increasing evidence shows that protein phosphorylation on serine, threonine and tyrosine residues is a major regulatory post-translational modification in the bacteria. This review focuses on the implications of bacterial phosphoproteome in bacterial pathogenicity and highlights recent development of methods in phosphoproteomics and the connectivity of the phosphorylation networks. Recent technical developments in the high accuracy mass spectrometry have dramatically transformed proteomics and made it possible the characterization of a few exhaustive site-specific bacterial phosphoproteomes. The high abundance of tyrosine phosphorylations in a few bacterial phosphoproteomes suggests their roles in the pathogenicity, especially in the case of pathogen-host interactions; the high abundance of multi-phosphorylation sites in bacterial phosphoprotein is a compensation of the relatively small phosphorylation size and an indicator of the delicate regulation of protein functions.
Topics: Bacteria; Bacterial Proteins; Host-Pathogen Interactions; Phosphoproteins; Phosphorylation; Proteomics; Tyrosine
PubMed: 22196355
DOI: 10.1016/S1672-0229(11)60015-6 -
Accounts of Chemical Research Feb 2013In proteins, the nitration of tyrosine residues to 3-nitro-tyrosine represents an oxidative post-translational modification that disrupts nitric oxide ((•)NO)...
In proteins, the nitration of tyrosine residues to 3-nitro-tyrosine represents an oxidative post-translational modification that disrupts nitric oxide ((•)NO) signaling and skews metabolism towards pro-oxidant processes. Indeed, excess levels of reactive oxygen species in the presence of (•)NO or (•)NO-derived metabolites lead to the formation of nitrating species such as peroxynitrite. Thus, protein 3-nitrotyrosine has been established as a biomarker of cell, tissue, and systemic "nitroxidative stress". Moreover, tyrosine nitration modifies key properties of the amino acid: phenol group pK(a), redox potential, hydrophobicity, and volume. Thus, the incorporation of a nitro group (-NO(2)) into protein tyrosines can lead to profound structural and functional changes, some of which contribute to altered cell and tissue homeostasis. In this Account, I describe our current efforts to define (1) biologically-relevant mechanisms of protein tyrosine nitration and (2) how this modification can cause changes in protein structure and function at the molecular level. First, I underscore the relevance of protein tyrosine nitration via free-radical-mediated reactions (in both peroxynitrite-dependent and -independent pathways) involving a tyrosyl radical intermediate (Tyr(•)). This feature of the nitration process is critical because Tyr(•) can follow various fates, including the formation of 3-nitrotyrosine. Fast kinetic techniques, electron paramagnetic resonance (EPR) studies, bioanalytical methods, and kinetic simulations have all assisted in characterizing and fingerprinting the reactions of tyrosine with peroxynitrite and one-electron oxidants and its further evolution to 3-nitrotyrosine. Recent findings show that nitration of tyrosines in proteins associated with biomembranes is linked to the lipid peroxidation process via a connecting reaction that involves the one-electron oxidation of tyrosine by lipid peroxyl radicals (LOO(•)). Second, immunochemical and proteomic-based studies indicate that protein tyrosine nitration is a selective process in vitro and in vivo, preferentially directed to a subset of proteins, and within those proteins, typically one or two tyrosine residues are site-specifically modified. The nature and site(s) of formation of the proximal oxidizing or nitrating species, the physicochemical characteristics of the local microenvironment, and the structural features of the protein account for part of this selectivity. How this relatively subtle chemical modification in one tyrosine residue can sometimes cause dramatic changes in protein activity has remained elusive. Herein, I analyze recent structural biology data of two pure and homogenously nitrated mitochondrial proteins (i.e., cytochrome c and manganese superoxide dismutase, MnSOD) to illustrate regioselectivity and structural effects of tyrosine nitration and subsequent impact in protein loss- or even gain-of-function.
Topics: Free Radicals; Lipid Peroxidation; Models, Molecular; Superoxides; Tyrosine
PubMed: 23157446
DOI: 10.1021/ar300234c -
IUBMB Life Oct 2007Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a... (Review)
Review
Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. An important issue is whether the human body is equipped with mechanisms to counteract the potentially harmful effects of nitrotyrosine. Sulfate conjugation, as mediated by the cytosolic sulfotransferases (SULTs), is widely used for the biotransformation and disposal of a variety of drugs and other xenobiotics, as well as endogenous thyroid/steroid hormones and catecholamine neurotransmitters. Recent studies have revealed that the sulfation of nitrotyrosine occurs in cells under oxidative/nitrative stress, and have pinpointed the SULT1A3 as the responsible SULT enzyme. In this review, we summarized the available information concerning the biochemistry of nitrotyrosine sulfation and the effects of genetic polymorphisms on the nitrotyrosine sulfating activity of SULT1A3. Functional implications of the sulfation of nitrotyrosine are discussed.
Topics: Animals; Arylsulfotransferase; Humans; Sulfates; Sulfotransferases; Tyrosine
PubMed: 17891604
DOI: 10.1080/15216540701589320 -
Free Radical Biology & Medicine Jan 2016During inflammation, leukocyte-derived eosinophil peroxidase catalyses the formation of hypobromous acid, which can brominate tyrosine residues in proteins to form...
During inflammation, leukocyte-derived eosinophil peroxidase catalyses the formation of hypobromous acid, which can brominate tyrosine residues in proteins to form bromotyrosine. Since eosinophils are involved in the pathogenesis of allergic reactions, such as asthma, urinary bromotyrosine level has been used for the assessment of children with asthma. However, little is known about the metabolism and disposition of bromotyrosine in vivo. The aim of this study was to identify the major urinary metabolites formed during bromotyrosine metabolism and to develop mass spectrometric methods for their quantitation. Deuterium-labeled bromotyrosine was synthesized by deuterium exchange. [D3]bromotyrosine (500 nmole) was injected intraperitoneally into Sprague-Dawley rats and urine was collected for 24h in a metabolic cage. (13)C-labeled derivatives of bromotyrosine and its major urinary metabolite were synthesized and used as internal standards for quantitation. Following solid phase extraction, urine samples were derivatized to the pentafluorobenzyl ester, and analyzed using isotope dilution gas chromatography and negative-ion chemical ionization mass spectrometry. A novel brominated metabolite, 3-bromo-4-hydroxyphenylacetic acid (bromo-HPA), was identified as the major brominated metabolite of bromotyrosine. Bromo-HPA only accounted for 0.43 ± 0.04% of infused [D3]bromotyrosine and 0.12 ± 0.02% of infused [D3]bromotyrosine was excreted in the urine unchanged. However, ~1.3% (6.66 ± 1.33 nmole) of infused [D3]bromotyrosine was excreted in the urine as the de-brominated metabolite, [D3]4-hydroxyphenylacetic acid, which is also a urinary metabolite of tyrosine in mammals. We also tested whether or not iodotyrosine dehalogenase can catalyse de-bromination of bromotyrosine and showed that iodotyrosine dehalogenase is able to de-brominate free bromotyrosine in vitro. We identified bromo-HPA as the main brominated urinary metabolite of bromotyrosine in rats. However, de-halogenation of bromotyrosine is the major metabolic pathway to eliminate free brominated tyrosine in vivo.
Topics: Animals; Bromine; Deuterium; Gas Chromatography-Mass Spectrometry; Male; Phenylacetates; Rats; Rats, Sprague-Dawley; Tyrosine
PubMed: 26638695
DOI: 10.1016/j.freeradbiomed.2015.11.030 -
Organic Letters Aug 2021Isotopically labeled amino acids are widely used to study the structure and dynamics of proteins by NMR. Herein we describe a facile, gram-scale synthesis of compounds...
Isotopically labeled amino acids are widely used to study the structure and dynamics of proteins by NMR. Herein we describe a facile, gram-scale synthesis of compounds and under standard laboratory conditions from the common intermediate . is obtained via simple deprotection, while is accessed through a reductive deoxygenation/deuteration sequence and deprotection. and provide improved signal intensity using lower amounts of labeled precursor and are alternatives to existing labeling approaches.
Topics: Amino Acids; Isotope Labeling; Magnetic Resonance Spectroscopy; Molecular Structure; Phenylalanine; Proteins; Tyrosine
PubMed: 34379431
DOI: 10.1021/acs.orglett.1c02084 -
Biochimica Et Biophysica Acta Jan 2015In bioenergetic reactions, electrons are transferred long distances via a hopping mechanism. In photosynthesis and DNA synthesis, the aromatic amino acid residue,... (Review)
Review
In bioenergetic reactions, electrons are transferred long distances via a hopping mechanism. In photosynthesis and DNA synthesis, the aromatic amino acid residue, tyrosine, functions as an intermediate that is transiently oxidized and reduced during long distance electron transfer. At physiological pH values, oxidation of tyrosine is associated with a deprotonation of the phenolic oxygen, giving rise to a proton coupled electron transfer (PCET) reaction. Tyrosine-based PCET reactions are important in photosystem II, which carries out the light-induced oxidation of water, and in ribonucleotide reductase, which reduces ribonucleotides to form deoxynucleotides. Photosystem II contains two redox-active tyrosines, YD (Y160 in the D2 polypeptide) and YZ (Y161 in the D1 polypeptide). YD forms a light-induced stable radical, while YZ functions as an essential charge relay, oxidizing the catalytic Mn₄CaO₅ cluster on each of four photo-oxidation reactions. In Escherichia coli class 1a RNR, the β2 subunit contains the radical initiator, Y122O•, which is reversibly reduced and oxidized in long range electron transfer with the α2 subunit. In the isolated E. coli β2 subunit, Y122O• is a stable radical, but Y122O• is activated for rapid PCET in an α2β2 substrate/effector complex. Recent results concerning the structure and function of YD, YZ, and Y122 are reviewed here. Comparison is made to recent results derived from bioengineered proteins and biomimetic compounds, in which tyrosine-based charge transfer mechanisms have been investigated. This article is part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic systems.
Topics: Amino Acid Sequence; Biomimetics; DNA; Electron Transport; Electrons; Energy Metabolism; Models, Molecular; Molecular Sequence Data; Oxidation-Reduction; Photosystem II Protein Complex; Protein Engineering; Protons; Tyrosine
PubMed: 25260243
DOI: 10.1016/j.bbabio.2014.09.003 -
ENeuro 2018The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young... (Randomized Controlled Trial)
Randomized Controlled Trial
The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young adults, especially during high environmental demands. Tyrosine administration might also affect catecholamine transmission in the aging brain, thereby improving cognitive functioning. In healthy older adults, impairments have been demonstrated in two forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing) under high information load. However, no study has directly compared the effects of a catecholamine precursor on reactive and load-dependent proactive inhibition. In this study we explored the effects of tyrosine on reactive and proactive response inhibition and signal in dopaminergically innervated fronto-striatal regions. Depending on age, tyrosine might lead to beneficial or detrimental neurocognitive effects. We aimed to address these hypotheses in 24 healthy older human adults (aged 61-72 years) using fMRI in a double blind, counterbalanced, placebo-controlled, within-subject design. Across the group, tyrosine did not alter reactive or proactive inhibition behaviorally but did increase fronto-parietal proactive inhibition-related activation. When taking age into account, tyrosine affected proactive inhibition both behaviorally and neurally. Specifically, increasing age was associated with a greater detrimental effect of tyrosine compared with placebo on proactive slowing. Moreover, with increasing age, tyrosine decreased fronto-striatal and parietal proactive signal, which correlated positively with tyrosine's effects on proactive slowing. Concluding, tyrosine negatively affected proactive response slowing and associated fronto-striatal activation in an age-dependent manner, highlighting the importance of catecholamines, perhaps particularly dopamine, for proactive response inhibition in older adults.
Topics: Aged; Aging; Anticipation, Psychological; Double-Blind Method; Executive Function; Female; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term; Middle Aged; Parietal Lobe; Prefrontal Cortex; Proactive Inhibition; Psychomotor Performance; Putamen; Reactive Inhibition; Tyrosine
PubMed: 30094335
DOI: 10.1523/ENEURO.0035-17.2018