A5040316250- Neurological disorders and treatments
- Botulinum Toxin and Related Neurological Disorders
- Enzyme Structure and Function
- Heat shock proteins research
- Hereditary Neurological Disorders
- Protein Structure and Dynamics
- Ophthalmology and Eye Disorders
- Cancer Treatment and Pharmacology
- Glycosylation and Glycoproteins Research
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Bacillus and Francisella bacterial research
- Antimicrobial Peptides and Activities
- Mesoporous Materials and Catalysis
- Cancer Mechanisms and Therapy
- Pain Mechanisms and Treatments
- Blood properties and coagulation
- Supramolecular Self-Assembly in Materials
- RNA and protein synthesis mechanisms
- MXene and MAX Phase Materials
- Peptidase Inhibition and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Antibiotic Resistance in Bacteria
- Boron Compounds in Chemistry
- Cellular transport and secretion
Ipsen (United Kingdom)
2016-2022
Space Syntax (United Kingdom)
2014
Evotec (United Kingdom)
2009-2012
Peptide deformylase (PDF) is an essential bacterial metalloenzyme which deformylates the N-formylmethionine of newly synthesized polypeptides and as such represents a novel target for antibacterial chemotherapy. To identify PDF inhibitors, we screened inhibitor library identified N-formyl-hydroxylamine derivative, BB-3497, related natural hydroxamic acid antibiotic, actinonin, potent selective inhibitors PDF. elucidate interactions that contribute to binding affinity these determined crystal...
ABSTRACT Lipid A is the hydrophobic anchor of lipopolysaccharide (LPS) and forms major lipid component outer monolayer membrane gram-negative bacteria. required for bacterial growth virulence, inhibition its biosynthesis lethal to UDP-3- O -( R -3-hydroxymyristoyl)- N -acetylglucosamine deacetylase (LpxC) a metalloenzyme that catalyzes second step in A. Inhibitors LpxC have previously been shown antibiotic activities. We screened inhibitor library antibacterial activities against an...
Human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed) self-associate to form high-molecular mass aggregates. To explore the biological significance of chemokine aggregation, nonaggregating variants were sought. The phenotypes 105 hMIP-1alpha generated by systematic mutagenesis expression in yeast determined. residues Asp26 Glu66 critical self-association process. Substitution at either residue resulted...
Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression have been found to be associated with Huntington's disease (HD); specifically, up-regulated in the brains of HD patients animal models disease. Interestingly, genetic deletion two different mouse models, R6/1 R6/2, results improved phenotypes including reduction neuronal...
Botulinum neurotoxin B is a Food and Drug Administration-approved therapeutic toxin. However, it has lower binding affinity toward the human version of its major receptor, synaptotagmin II (h-Syt II), compared to mouse Syt II, because residue difference. Increasing h-Syt may improve botulinum B's efficacy reduce adverse effects. Here we utilized bacterial adenylate cyclase two-hybrid method carried out saturation mutagenesis screen in II-binding pocket B. The identifies E1191 as key residue:...
We report the preclinical characterization of two engineered botulinum neurotoxin serotype B proteins with significant therapeutic potential.
The Mapkap kinases 2 and 3 (MK2 MK3) have been implicated in intracellular signaling pathways leading to the production of pro-inflammatory cytokine tumor necrosis factor alpha. MK2 has pursued by biopharmaceutical industry for many years development a small molecule anti-inflammatory treatment drug-like inhibitors described. some these compounds, however, slowed absence high-resolution crystal structure MK2. Herein we present (1.9 A) highly homologous MK3 complex with pharmaceutical lead...
Botulinum neurotoxins (BoNTs) are used extensively as therapeutic agents. Serotypes A and B available marketed products. Higher doses of BoNT/B required to reach an efficacy similar that products containing BoNT/A. Advances in our understanding mechanism action have afforded the opportunity make rational modifications toxin aimed at increasing its activity. Recently, a mutation light chain (S201P) was described increases catalytic activity isolated biochemical assays. In this study, we...
ABSTRACT Bacterial toxins are able to act on neurons modulate signaling and function. Here, we find that nociceptive sensory mediate pain enriched in the receptor for anthrax toxins, ANTXR2. Anthrax Edema Toxin (ET) induced cAMP PKA Nav1.8 + modulated vivo . Peripherally administered ET mediated mechanical allodynia naïve mice during B. anthracis infection. Intrathecally produced analgesic effects, potently blocking pain-like behaviors multiple mouse models of inflammatory chronic...