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Current Biology : CB Feb 2020Melanins are a unique class of pigments found throughout the biosphere with a wide variety of functions, structures, and presentations. Cordero and Casadevall highlight...
Melanins are a unique class of pigments found throughout the biosphere with a wide variety of functions, structures, and presentations. Cordero and Casadevall highlight the wide range of places melanins are found and the diverse functions they play in nature.
Topics: Melanins
PubMed: 32097632
DOI: 10.1016/j.cub.2019.12.042 -
Science (New York, N.Y.) Jun 2019The human gut microbiota metabolizes the Parkinson's disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, the...
The human gut microbiota metabolizes the Parkinson's disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacterial l-dopa metabolism. Conversion of l-dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from is followed by transformation of dopamine to -tyramine by a molybdenum-dependent dehydroxylase from These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbial l-dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson's patient microbiotas and increases l-dopa bioavailability in mice.
Topics: Actinobacteria; Animals; Antiparkinson Agents; Bacterial Proteins; Decarboxylation; Dopamine; Enterococcus faecalis; Gastrointestinal Microbiome; Genome, Bacterial; HeLa Cells; Humans; Levodopa; Male; Metabolic Networks and Pathways; Mice, Inbred BALB C; Tyrosine; Tyrosine Decarboxylase
PubMed: 31196984
DOI: 10.1126/science.aau6323 -
Journal of the International Society of... Nov 2019A limited amount of research has demonstrated beneficial effects of caffeine and theanine supplementation for enhancement of mental performance. The purpose of this... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A limited amount of research has demonstrated beneficial effects of caffeine and theanine supplementation for enhancement of mental performance. The purpose of this investigation was to determine whether the acute ingestion of a supplement containing caffeine, theanine and tyrosine improves mental and physical performance in athletes.
METHODS
Twenty current or former male collegiate athletes (age: 20.5 ± 1.4 y; height: 1.82 ± 0.08 m; weight: 83.9 ± 12.6 kg; body fat: 13.8 ± 5.6%) completed this randomized, double-blind, placebo-controlled crossover trial. After familiarization, each participant completed two identical testing sessions with provision of a proprietary dietary supplement (SUP) containing caffeine theanine and tyrosine or a placebo (PL). Within each testing session, participants completed assessments of mental and physical performance before and after provision of SUP or PL, as well as after two rounds of exercise. Assessments were performed using a performance testing device (Makoto Arena) that evaluated multiple aspects of mental and physical performance in response to auditory and visual stimuli. Testing was performed both with the body in a static position and during dynamic movement. General linear models were used to evaluate the effects of SUP and PL on performance.
RESULTS
Changes in movement accuracy during performance assessment were greater following SUP ingestion as compared to PL for both static and dynamic testing (SUP: + 0.4 to 7.5%; PL: - 1.4 to 1.4% on average; p < 0.05). For dynamic testing, the change in number of targets hit was higher and the change in average hit time was lower with SUP as compared to PL (p < 0.05). However, there were no differences between conditions for the changes in number of targets hit or average hit time during static testing. There were no differences in changes of subjective variables during either condition, and performance measures during the two rounds of exercise did not differ between conditions (p > 0.05).
DISCUSSION
The present results indicate that a combination of a low-dose of caffeine with theanine and tyrosine may improve athletes' movement accuracy surrounding bouts of exhaustive exercise without altering subjective variables. Based on this finding, supplementation with caffeine, theanine and tyrosine could potentially hold ergogenic value for athletes in sports requiring rapid and accurate movements.
TRIAL REGISTRATION
NCT03019523. Registered 24 January 2017.
Topics: Athletic Performance; Caffeine; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Glutamates; Humans; Male; Performance-Enhancing Substances; Tyrosine; Young Adult
PubMed: 31771598
DOI: 10.1186/s12970-019-0326-3 -
Signal Transduction and Targeted Therapy Sep 2022Protein tyrosine kinases (PTKs) are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways.... (Review)
Review
Protein tyrosine kinases (PTKs) are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation of PTKs caused by various factors can deviate cell function from the expected trajectory to an abnormal growth state, leading to carcinogenesis. Inhibiting the aberrant PTK function could inhibit tumor growth. Therefore, tyrosine kinase inhibitors (TKIs), target-specific inhibitors of PTKs, have been used in treating malignant tumors and play a significant role in targeted therapy of cancer. Currently, drug resistance is the main reason for limiting TKIs efficacy of cancer. The increasing studies indicated that tumor microenvironment, cell death resistance, tumor metabolism, epigenetic modification and abnormal metabolism of TKIs were deeply involved in tumor development and TKI resistance, besides the abnormal activation of PTK-related signaling pathways involved in gene mutations. Accordingly, it is of great significance to study the underlying mechanisms of TKIs resistance and find solutions to reverse TKIs resistance for improving TKIs efficacy of cancer. Herein, we reviewed the drug resistance mechanisms of TKIs and the potential approaches to overcome TKI resistance, aiming to provide a theoretical basis for improving the efficacy of TKIs.
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Humans; Neoplasms; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Tumor Microenvironment; Tyrosine
PubMed: 36115852
DOI: 10.1038/s41392-022-01168-8 -
Science (New York, N.Y.) Dec 2022Peroxisomes are ubiquitous organelles whose dysfunction causes fatal human diseases. Most peroxisomal proteins are imported from the cytosol in a folded state by the...
Peroxisomes are ubiquitous organelles whose dysfunction causes fatal human diseases. Most peroxisomal proteins are imported from the cytosol in a folded state by the soluble receptor PEX5. How folded cargo crosses the membrane is unknown. Here, we show that peroxisomal import is similar to nuclear transport. The peroxisomal membrane protein PEX13 contains a conserved tyrosine (Y)- and glycine (G)-rich YG domain, which forms a selective phase resembling that formed by phenylalanine-glycine (FG) repeats within nuclear pores. PEX13 resides in the membrane in two orientations that oligomerize and suspend the YG meshwork within the lipid bilayer. Purified YG domains form hydrogels into which PEX5 selectively partitions, by using conserved aromatic amino acid motifs, bringing cargo along. The YG meshwork thus forms an aqueous conduit through which PEX5 delivers folded proteins into peroxisomes.
Topics: Humans; Glycine; Nuclear Pore; Peroxisomes; Protein Transport; Membrane Proteins; Conserved Sequence; Protein Domains; Tyrosine
PubMed: 36520918
DOI: 10.1126/science.adf3971 -
FEMS Microbiology Reviews Aug 2021The integration of mobile genetic elements into their host chromosome influences the immediate fate of cellular organisms and gradually shapes their evolution.... (Review)
Review
The integration of mobile genetic elements into their host chromosome influences the immediate fate of cellular organisms and gradually shapes their evolution. Site-specific recombinases catalyzing this integration have been extensively characterized both in bacteria and eukarya. More recently, a number of reports provided the in-depth characterization of archaeal tyrosine recombinases and highlighted new particular features not observed in the other two domains. In addition to being active in extreme environments, archaeal integrases catalyze reactions beyond site-specific recombination. Some of these integrases can catalyze low-sequence specificity recombination reactions with the same outcome as homologous recombination events generating deep rearrangements of their host genome. A large proportion of archaeal integrases are termed suicidal due to the presence of a specific recombination target within their own gene. The paradoxical maintenance of integrases that disrupt their gene upon integration implies novel mechanisms for their evolution. In this review, we assess the diversity of the archaeal tyrosine recombinases using a phylogenomic analysis based on an exhaustive similarity network. We outline the biochemical, ecological and evolutionary properties of these enzymes in the context of the families we identified and emphasize similarities and differences between archaeal recombinases and their bacterial and eukaryal counterparts.
Topics: Archaea; Eukaryota; Integrases; Recombinases; Tyrosine
PubMed: 33524101
DOI: 10.1093/femsre/fuab004 -
Current Opinion in Allergy and Clinical... Dec 2022The purpose of this article is to provide an overview of the literature pertaining to the use of MicroCrystalline Tyrosine (MCT) in the immunotherapy with an emphasis on... (Review)
Review
PURPOSE OF REVIEW
The purpose of this article is to provide an overview of the literature pertaining to the use of MicroCrystalline Tyrosine (MCT) in the immunotherapy with an emphasis on recent developments.
RECENT FINDINGS
In addition to significant effectiveness and safety profiles, additional aspects of interest such as booster immunotherapy concepts, sustained clinical effects, long-term efficacy and disease-modifying effects are being focused on in the recently published studies. The depot adjuvant MCT also shows potential in promising disease-challenge models such as for malaria and melanoma.
SUMMARY
MCT-adsorbed immunotherapy products have been shown to provide convincing overall safety, tolerability and efficacy outcomes, as well in vulnerable groups such as children and asthmatic patients.
Topics: Child; Humans; Tyrosine; Immunotherapy; Adjuvants, Immunologic; Immunologic Factors; Asthma
PubMed: 36254926
DOI: 10.1097/ACI.0000000000000859 -
Science (New York, N.Y.) Feb 2020Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance...
Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance spectroscopy, small-angle x-ray scattering, and multiscale simulations, we have uncovered sequence features that determine the overall phase behavior of PLDs. We show that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions. The valence of aromatic residues also determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense phases as a function of temperature. We also show that uniform patterning of aromatic residues is a sequence feature that promotes LLPS while inhibiting aggregation. Our findings lead to the development of a numerical stickers-and-spacers model that enables predictions of full binodals of PLDs from their sequences.
Topics: Amino Acid Sequence; Heterogeneous Nuclear Ribonucleoprotein A1; Magnetic Resonance Spectroscopy; Phase Transition; Phenylalanine; Prions; Protein Domains; Scattering, Small Angle; Tyrosine; X-Ray Diffraction
PubMed: 32029630
DOI: 10.1126/science.aaw8653 -
Organic & Biomolecular Chemistry Jan 2020Tyrosine phosphorylation is a critical component of signal transduction for multicellular organisms, particularly for pathways that regulate cell proliferation and... (Review)
Review
Tyrosine phosphorylation is a critical component of signal transduction for multicellular organisms, particularly for pathways that regulate cell proliferation and differentiation. While tyrosine kinase inhibitors have become FDA-approved drugs, inhibitors of the other important components of these signaling pathways have been harder to develop. Specifically, direct phosphotyrosine (pTyr) isosteres have been aggressively pursued as inhibitors of Src homology 2 (SH2) domains and protein tyrosine phosphatases (PTPs). Medicinal chemists have produced many classes of peptide and small molecule inhibitors that mimic pTyr. However, balancing affinity with selectivity and cell penetration has made this an extremely difficult space for developing successful clinical candidates. This review will provide a comprehensive picture of the field of pTyr isosteres, from early beginnings to the current state and trajectory. We will also highlight the major protein targets of these medicinal chemistry efforts, the major classes of peptide and small molecule inhibitors that have been developed, and the handful of compounds which have been tested in clinical trials.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Line, Tumor; Humans; Peptidomimetics; Phosphotyrosine; Protein Tyrosine Phosphatases; Transcription Factors; src Homology Domains
PubMed: 31777907
DOI: 10.1039/c9ob01998g -
Annals of Medicine Dec 2023Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition... (Review)
Review
Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition site of GP IIb/IIIa to prevent platelet aggregation. It reduces the incidence of thrombotic cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Although generally considered safe, tirofiban has been reported to be associated with thrombocytopenia in several case reports and clinical trials. The pathogenesis for this adverse reaction is not entirely understood, is thought to be due to immune-mediated reaction. This side effect caused by tirofiban is especially concerning given how frequently it is used in the practice of contemporary cardiovascular care. The present review provides an overview of the pathophysiology, clinical presentation, management, and risk factors associated with tirofiban-induced thrombocytopenia.
Topics: Humans; Tirofiban; Platelet Aggregation Inhibitors; Tyrosine; Thrombocytopenia; Platelet Glycoprotein GPIIb-IIIa Complex; Acute Coronary Syndrome
PubMed: 37439782
DOI: 10.1080/07853890.2023.2233425