Brian C. Smith
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View article: BET bromodomain inhibitors attenuate transcription of a subset of IL-1-induced NF-κB targets that promote inflammation in β-cells
BET bromodomain inhibitors attenuate transcription of a subset of IL-1-induced NF-κB targets that promote inflammation in β-cells Open
View article: The Big Review VI: Carbonyl Compounds
The Big Review VI: Carbonyl Compounds Open
Carbonyl containing functional groups are strong infrared absorbers and a number of them are easy to identify by infrared spectroscopy. Here, we will review the spectra of ketone and carboxylic acids.
View article: Abstract 2156 Epigenetic Control of Macrophage Inflammatory Activation by the Bromodomain and Extraterminal Domain Proteins
Abstract 2156 Epigenetic Control of Macrophage Inflammatory Activation by the Bromodomain and Extraterminal Domain Proteins Open
View article: Oxidized LDL stimulates PKM2-mediated mtROS production and phagocytosis
Oxidized LDL stimulates PKM2-mediated mtROS production and phagocytosis Open
Oxidized low-density lipoprotein (oxLDL) promotes proatherogenic phenotypes in macrophages, accelerating the progression of atherosclerosis. Our previous studies demonstrated that oxLDL binds to its receptor CD36, stimulating mitochondrial…
View article: Reutericyclin, a specialized metabolite of <i>Limosilactobacillus reuteri</i> , mitigates risperidone-induced weight gain in mice
Reutericyclin, a specialized metabolite of <i>Limosilactobacillus reuteri</i> , mitigates risperidone-induced weight gain in mice Open
The role of xenobiotic disruption of microbiota, corresponding dysbiosis, and potential links to host metabolic diseases are of critical importance. In this study, we used a widely prescribed antipsychotic drug, risperidone, known to influ…
View article: Role of SIRT3 in the regulation of Gadd45α expression and DNA repair in β-cells
Role of SIRT3 in the regulation of Gadd45α expression and DNA repair in β-cells Open
In previous studies, we have shown that growth arrest and DNA damage (Gadd) 45α is required for the repair of nitric oxide-mediated DNA damage in β-cells. Gadd45α expression is stimulated by nitric oxide and requires forkhead box protein (…
View article: Multivalent nucleosome scaffolding by bromodomain and extraterminal domain tandem bromodomains
Multivalent nucleosome scaffolding by bromodomain and extraterminal domain tandem bromodomains Open
Promoter-promoter and enhancer-promoter interactions are enriched in histone acetylation and central to chromatin organization in active genetic regions. Bromodomains are epigenetic "readers" that recognize and bind histone acetylation. Br…
View article: Inhibition of Sirtuin Deacylase Activity by Peroxynitrite
Inhibition of Sirtuin Deacylase Activity by Peroxynitrite Open
Sirtuins are a class of enzymes that deacylate protein lysine residues using NAD+ as a cosubstrate. Sirtuin deacylase activity has been historically regarded as protective; loss of sirtuin deacylase activity potentially increase…
View article: Lipid Trolling to Optimize A<sub>3</sub> Adenosine Receptor-Positive Allosteric Modulators (PAMs)
Lipid Trolling to Optimize A<sub>3</sub> Adenosine Receptor-Positive Allosteric Modulators (PAMs) Open
A3 adenosine receptor (A3AR) positive allosteric modulators (PAMs) (2,4-disubstituted-1H-imidazo[4,5-c]quinolin-4-amines) allosterically increase the Emax of A3AR agonists, b…
View article: Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types
Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types Open
Inhibition of BET bromodomains is a novel potential strategy to prevent and treat diabetes mellitus. However, BET inhibitors have negative side effects. We synthesized a BET inhibitor expected to exploit the high zinc concentration in β ce…
View article: Cancer-associated polybromo-1 bromodomain 4 missense variants variably impact bromodomain ligand binding and cell growth suppression
Cancer-associated polybromo-1 bromodomain 4 missense variants variably impact bromodomain ligand binding and cell growth suppression Open
View article: Current Trends in Sirtuin Activator and Inhibitor Development
Current Trends in Sirtuin Activator and Inhibitor Development Open
Sirtuins are NAD+-dependent protein deacylases and key metabolic regulators, coupling the cellular energy state with selective lysine deacylation to regulate many downstream cellular processes. Humans encode seven sirtuin isoforms (Sirt1-7…
View article: Extrahelical Binding Site for a 1H-Imidazo[4,5-c]quinolin-4-amine A3 Adenosine Receptor Positive Allosteric Modulator on Helix 8 and Distal Portions of Transmembrane Domains 1 and 7
Extrahelical Binding Site for a 1H-Imidazo[4,5-c]quinolin-4-amine A3 Adenosine Receptor Positive Allosteric Modulator on Helix 8 and Distal Portions of Transmembrane Domains 1 and 7 Open
View article: Identification of Protein Targets of <i>S</i>-Nitroso-Coenzyme A-Mediated <i>S</i>-Nitrosation Using Chemoproteomics
Identification of Protein Targets of <i>S</i>-Nitroso-Coenzyme A-Mediated <i>S</i>-Nitrosation Using Chemoproteomics Open
S-Nitrosation is a cysteine post-translational modification fundamental to cellular signaling. This modification regulates protein function in numerous biological processes in the nervous, cardiovascular, and immune systems. Small m…
View article: Deep computational phenotyping of genomic variants impacting the SET domain of KMT2C reveal molecular mechanisms for their dysfunction
Deep computational phenotyping of genomic variants impacting the SET domain of KMT2C reveal molecular mechanisms for their dysfunction Open
Introduction: Kleefstra Syndrome type 2 (KLEFS-2) is a genetic, neurodevelopmental disorder characterized by intellectual disability, infantile hypotonia, severe expressive language delay, and characteristic facial appearance, with a spect…
View article: Oxidized LDL regulates efferocytosis through the CD36-PKM2-mtROS pathway
Oxidized LDL regulates efferocytosis through the CD36-PKM2-mtROS pathway Open
Macrophage efferocytosis, the process by which phagocytes engulf and remove apoptotic cells (ACs), plays a critical role in maintaining tissue homeostasis. Efficient efferocytosis prevents secondary necrosis, mitigates chronic inflammation…
View article: A Multi-Layered Computational Structural Genomics Approach Enhances Domain-Specific Interpretation of Kleefstra Syndrome Variants in EHMT1
A Multi-Layered Computational Structural Genomics Approach Enhances Domain-Specific Interpretation of Kleefstra Syndrome Variants in EHMT1 Open
This study investigates the functional significance of assorted variants of uncertain significance (VUS) in euchromatic histone lysine methyltransferase 1 (EHMT1), which is critical for early development and normal physiology. EHMT1 mutati…
View article: Rational Design and Development of Selective BRD7 Bromodomain Inhibitors and Their Activity in Prostate Cancer
Rational Design and Development of Selective BRD7 Bromodomain Inhibitors and Their Activity in Prostate Cancer Open
Bromodomain-containing proteins are readers of acetylated lysine and play important roles in cancer. Bromodomain-containing protein 7 (BRD7) is implicated in multiple malignancies; however, there are no selective chemical probes to study i…
View article: Synthesis of fluorinated triphenylphosphonium analogs that improve cancer cell selectivity and in vivo detection
Synthesis of fluorinated triphenylphosphonium analogs that improve cancer cell selectivity and in vivo detection Open
View article: Cysteine and methionine oxidation in thrombotic disorders
Cysteine and methionine oxidation in thrombotic disorders Open
View article: Beyond Structural Bioinformatics for Genomics with Dynamics Characterization of an Expanded KRAS Mutational Landscape
Beyond Structural Bioinformatics for Genomics with Dynamics Characterization of an Expanded KRAS Mutational Landscape Open
Current capabilities in genomic sequencing outpace functional interpretations. Our previous work showed that 3D protein structure calculations enhance mechanistic understanding of genetic variation in sequenced tumors and patients with rar…
View article: Sulfenylation links oxidative stress to protein disulfide isomerase oxidase activity and thrombus formation
Sulfenylation links oxidative stress to protein disulfide isomerase oxidase activity and thrombus formation Open
View article: Harnessing the Noncanonical Keap1-Nrf2 Pathway for Human Cytomegalovirus Control
Harnessing the Noncanonical Keap1-Nrf2 Pathway for Human Cytomegalovirus Control Open
Antiviral treatment for human cytomegalovirus (HCMV) is limited and suffers from the selection of drug-resistant viruses. Several cellular pathways have been shown to modulate HCMV replication.
View article: Fragment-based drug discovery of small molecule ligands for the human chemokine CCL28
Fragment-based drug discovery of small molecule ligands for the human chemokine CCL28 Open
The mucosal chemokine CCL28 is a promising target for immunotherapy drug development due to its elevated expression level in epithelial cells and critical role in creating and maintaining an immunosuppressive tumor microenvironment. Using …
View article: Fragment-based screening by protein-detected NMR spectroscopy
Fragment-based screening by protein-detected NMR spectroscopy Open
View article: Analysis of continuous enzyme kinetic data using ICEKAT
Analysis of continuous enzyme kinetic data using ICEKAT Open
View article: A multi-layered computational structural genomics approach enhances domain-specific interpretation of Kleefstra syndrome variants in EHMT1
A multi-layered computational structural genomics approach enhances domain-specific interpretation of Kleefstra syndrome variants in EHMT1 Open
This study investigates the functional significance of assorted variants of uncertain significance (VUS) in euchromatic histone lysine methyltransferase 1 (EHMT1), which is critical for early development and normal physiology. EHMT1 mutati…
View article: Beyond structural bioinformatics for genomics with dynamics characterization of an expanded KRAS mutational landscape
Beyond structural bioinformatics for genomics with dynamics characterization of an expanded KRAS mutational landscape Open
Current capabilities in genomic sequencing outpace functional interpretations. Our previous work showed that 3D protein structure calculations enhance mechanistic understanding of genetic variation in sequenced tumors and patients with rar…
View article: Fluorinated triphenylphosphonium analogs improve cell selectivity and in vivo detection of mito-metformin
Fluorinated triphenylphosphonium analogs improve cell selectivity and in vivo detection of mito-metformin Open
View article: Pharmacological inhibition of the acetyltransferase Tip60 mitigates myocardial infarction injury
Pharmacological inhibition of the acetyltransferase Tip60 mitigates myocardial infarction injury Open
Pharmacologic strategies that target factors with both pro-apoptotic and anti-proliferative functions in cardiomyocytes (CMs) may be useful for the treatment of ischemic heart disease. One such multifunctional candidate for drug targeting …