Allosteric Regulation

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  Subject Areas on Research

  • 2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. 
  • A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation. 
  • A decade of caspases. 
  • ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells. 
  • Allosteric Inhibition of ABL Kinases: Therapeutic Potential in Cancer. 
  • Allosteric activation of proto-oncogene kinase Src by GPCR-beta-arrestin complexes. 
  • Allosteric cooperation in a de novo-designed two-domain protein. 
  • Allosteric effects on oxidative and nitrosative reactions of cell-free hemoglobins. 
  • Allosteric inhibition of kinesin-5 modulates its processive directional motility. 
  • Allosteric inhibitor of β-catenin selectively targets oncogenic Wnt signaling in colon cancer. 
  • Allosteric interactions in non-alpha chains isolated from normal human hemoglobin, fetal hemoglobin, and hemoglobin Abruzzo (beta143 (H21) His replaced by Arg). 
  • Allosteric intermediates indicate R2 is the liganded hemoglobin end state. 
  • Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestin. 
  • Allosteric modulation of Callinectes sapidus hemocyanin by binding of L-lactate. 
  • Allosteric modulation of nucleoporin assemblies by intrinsically disordered regions. 
  • Allosteric modulation of proteinase 3 activity by anti-neutrophil cytoplasmic antibodies in granulomatosis with polyangiitis. 
  • Allosteric modulation of β-arrestin-biased angiotensin II type 1 receptor signaling by membrane stretch. 
  • Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation. 
  • Allosteric regulation of estrogen receptor structure, function, and coactivator recruitment by different estrogen response elements. 
  • Allosteric regulation of type I hexokinase: A site-directed mutational study indicating location of the functional glucose 6-phosphate binding site in the N-terminal half of the enzyme. 
  • Allosteric transition intermediates modelled by crosslinked haemoglobins. 
  • Allostery in Callinectes sapidus hemocyanin: cooperative oxygen binding and interactions with L-lactate, calcium, and protons. 
  • An engineered liver glycogen phosphorylase with AMP allosteric activation. 
  • An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing. 
  • An equilibrium binding study of the interaction of aspartate transcarbamylase with cytidine 5'-triphosphate and adenosine 5'-triphosphate. 
  • An inhibitory region of the DNA-binding domain of thyroid hormone receptor blocks hormone-dependent transactivation. 
  • Ankyrin regulation: an alternatively spliced segment of the regulatory domain functions as an intramolecular modulator. 
  • Beta-arrestin-biased ligands at seven-transmembrane receptors. 
  • Biased Allosteric Modulators: New Frontiers in GPCR Drug Discovery. 
  • Biased G Protein-Coupled Receptor Signaling: Changing the Paradigm of Drug Discovery. 
  • Biased signalling: from simple switches to allosteric microprocessors. 
  • COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. 
  • Characterization of nucleotide binding sites on chloroplast coupling factor 1. 
  • Characterization of the ionizable groups interacting with anionic allosteric effectors of human hemoglobin. 
  • Characterization of two different five-coordinate soluble guanylate cyclase ferrous-nitrosyl complexes. 
  • Chloride and pH dependence of cooperative interactions in Limulus polyphemus hemocyanin. 
  • Chronic nicotine and dizocilpine effects on regionally specific nicotinic and NMDA glutamate receptor binding. 
  • Co-operative interactions between troponin-tropomyosin units extend the length of the thin filament in skeletal muscle. 
  • Coarse-grained modeling of allosteric regulation in protein receptors. 
  • Compensatory responses to pyruvate carboxylase suppression in islet beta-cells. Preservation of glucose-stimulated insulin secretion. 
  • Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor. 
  • Conversion of a maltose receptor into a zinc biosensor by computational design. 
  • Crystal structure of deoxygenated Limulus polyphemus subunit II hemocyanin at 2.18 A resolution: clues for a mechanism for allosteric regulation. 
  • Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. 
  • Crystallographic analysis of oxygenated and deoxygenated states of arthropod hemocyanin shows unusual differences. 
  • Design of bioelectronic interfaces by exploiting hinge-bending motions in proteins. 
  • Design, synthesis, and functional assessment of Cmpd-15 derivatives as negative allosteric modulators for the β2-adrenergic receptor. 
  • Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators. 
  • Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements. 
  • Divergent transducer-specific molecular efficacies generate biased agonism at a G protein-coupled receptor (GPCR). 
  • Domain-specific effector interactions within the central cavity of human adult hemoglobin in solution and in porous sol-gel matrices: evidence for long-range communication pathways. 
  • Dual allosteric modulation of opioid antinociceptive potency by α2A-adrenoceptors. 
  • Effect of oxygen and allosteric effects on structural stability of oligomeric hemocyanins of the arthropod, Limulus polyphemus, and the mollusc, Helix pomatia. 
  • Effects of S-nitrosation on oxygen binding by normal and sickle cell hemoglobin. 
  • Effects of a synthetic allosteric modifier of hemoglobin oxygen affinity on outcome from global cerebral ischemia in the rat. 
  • Efficiency, selectivity, and robustness of nucleocytoplasmic transport. 
  • Enhancer-origin interaction in plasmid R6K involves a DNA loop mediated by initiator protein. 
  • Escherichia coli purine repressor: key residues for the allosteric transition between active and inactive conformations and for interdomain signaling. 
  • Functional coupling of oxygen binding and vasoactivity in S-nitrosohemoglobin. 
  • G protein-coupled receptor kinases. 
  • Glutamate-binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts. 
  • Glutathione activates virulence gene expression of an intracellular pathogen. 
  • Glycine regulation of the N-methyl-D-aspartate receptor-gated ion channel in hippocampal membranes. 
  • How Gsalpha activates adenylyl cyclase. 
  • How the EcoRI endonuclease recognizes and cleaves DNA. 
  • Identification and characterization of the sodium-binding site of activated protein C. 
  • Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70. 
  • Identification of new batrachotoxin-sensing residues in segment IIIS6 of the sodium channel. 
  • Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors. 
  • Inhibition of prostate cancer cell growth by second-site androgen receptor antagonists. 
  • Interaction of aspartate transcarbamylase with 5-bromocytidine 5'-tri-, di-, and monophosphates. 
  • K channel subconductance levels result from heteromeric pore conformations. 
  • Kinetics of allosteric enzymes. 
  • L-glutamine D-fructose-6-P aminotransferase regulation by glucose-6-P and UDP-N-acetylglucosamine. 
  • Ligand interactions in the adenosine nucleotide-binding domain of the Hsp90 chaperone, GRP94. I. Evidence for allosteric regulation of ligand binding. 
  • Lipid molecules induce p38α activation via a novel molecular switch. 
  • Long-Range Allosteric Interactions between the Folate and Methionine Cycles Stabilize DNA Methylation Reaction Rate 
  • ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse. 
  • Manipulation of ligand binding affinity by exploitation of conformational coupling. 
  • Mechanism of corepressor-mediated specific DNA binding by the purine repressor. 
  • Mechanism of intracellular allosteric β2AR antagonist revealed by X-ray crystal structure. 
  • Mechanism of β2AR regulation by an intracellular positive allosteric modulator. 
  • Molecular mechanism of biased signaling in a prototypical G protein-coupled receptor. 
  • Multiple conformational changes in enzyme catalysis. 
  • Nitric-oxide synthase forms N-NO-pterin and S-NO-cys: implications for activity, allostery, and regulation. 
  • Nucleotide regulation of soluble guanylate cyclase substrate specificity. 
  • Oxygen binding by Limulus polyphemus hemocyanin: allosteric modulation by chloride ions. 
  • Probing the Allosteric Role of the α5 Subunit of α3β4α5 Nicotinic Acetylcholine Receptors by Functionally Selective Modulators and Ligands. 
  • RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system. 
  • Rational Design of Selective Allosteric Inhibitors of PHGDH and Serine Synthesis with Anti-tumor Activity. 
  • Receptor biophysics and biochemistry. Enzymes. 
  • Recombinant acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) purified to essential homogeneity utilizes cholesterol in mixed micelles or in vesicles in a highly cooperative manner. 
  • Regulation of intrasteric inhibition of the multifunctional calcium/calmodulin-dependent protein kinase. 
  • Regulation of the deleterious effects of binge-like exposure to alcohol during adolescence by α7 nicotinic acetylcholine receptor agents: prevention by pretreatment with a α7 negative allosteric modulator and emulation by a α7 agonist in alcohol-preferring (P) male and female rats. 
  • Relaxation spectra of aspartate transcarbamylase. Interaction of the native enzyme with an adenosine 5'-triphosphate analog. 
  • Relaxation spectra of aspartate transcarbamylase. Interaction of the native enzyme with cytidine 5'-triphosphate. 
  • S-Nitrosohemoglobin is unstable in the reductive erythrocyte environment and lacks O2/NO-linked allosteric function. 
  • S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. 
  • S-nitrosohemoglobin is distinguished from other nitrosovasodilators by unique oxygen-dependent responses that support an allosteric mechanism of action. 
  • Small-Molecule Positive Allosteric Modulators of the β2-Adrenoceptor Isolated from DNA-Encoded Libraries. 
  • Small-molecule inhibitors of integrin alpha2beta1 that prevent pathological thrombus formation via an allosteric mechanism. 
  • Soluble guanylate cyclase is activated differently by excess NO and by YC-1: resonance Raman spectroscopic evidence. 
  • Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in β-arrestin coupling. 
  • Stimulation of catecholamine-sensitive adenylate cyclase by 5'-guanylyl-imidodiphosphate. 
  • Structural basis for allosteric control of the transcription regulator CcpA by the phosphoprotein HPr-Ser46-P. 
  • Structural basis for the root effect in haemoglobin. 
  • Structural interconversions modulate activity of Escherichia coli ribonucleotide reductase. 
  • Studies of the copper and heme cofactors of pseudomonad L-tryptophan-2,3-dioxygenase by electron paramagnetic resonance spectroscopy. 
  • Substitutions in the domain III voltage-sensing module enhance the sensitivity of an insect sodium channel to a scorpion beta-toxin. 
  • Targeting Mutant PPM1D Sensitizes Diffuse Intrinsic Pontine Glioma Cells to the PARP Inhibitor Olaparib. 
  • The ABL2 kinase regulates an HSF1-dependent transcriptional program required for lung adenocarcinoma brain metastasis. 
  • The GPCR-β-arrestin complex allosterically activates C-Raf by binding its amino terminus. 
  • The NR1 M3 domain mediates allosteric coupling in the N-methyl-D-aspartate receptor. 
  • The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model 
  • The rational design of allosteric interactions in a monomeric protein and its applications to the construction of biosensors. 
  • The relative activity of "function sparing" HIV-1 entry inhibitors on viral entry and CCR5 internalization: is allosteric functional selectivity a valuable therapeutic property? 
  • The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 inhibits inflammatory pain-induced and incision-induced hypersensitivity in rat. 
  • Three-dimensional structure of calmodulin. 
  • Thrombomodulin increases the rate of thrombin inhibition by BPTI. 
  • Tropomyosin. Does resolution lead to reconciliation? 
  • Unique Positive Cooperativity Between the β-Arrestin-Biased β-Blocker Carvedilol and a Small Molecule Positive Allosteric Modulator of the β2-Adrenergic Receptor. 
  • gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. 
  • β-Arrestin-Biased Allosteric Modulator Potentiates Carvedilol-Stimulated β Adrenergic Receptor Cardioprotection. 
  • β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors. 
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  Keywords of People

  • Erickson, Harold Paul, James B. Duke Distinguished Professor of Cell Biology, Cell Biology
  • McDonnell, Donald Patrick, Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology, in the School of Medicine, Pharmacology & Cancer Biology