A5022968869- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
- Adenosine and Purinergic Signaling
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Enzyme Structure and Function
- Receptor Mechanisms and Signaling
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- Molecular Sensors and Ion Detection
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- Biochemical effects in animals
- Biochemical and Molecular Research
- RNA modifications and cancer
- Plant nutrient uptake and metabolism
- Metabolism and Genetic Disorders
- Folate and B Vitamins Research
- Digestive system and related health
University of Oxford
2015-2025
Kavli Energy NanoScience Institute
2024
Bioscience Research
2024
Alltech (Ireland)
2020
Cancer Research UK
2006-2013
GlobeImmune (United States)
2007
Goethe University Frankfurt
2007
University of St Andrews
2002-2006
University of Toledo Medical Center
2005
Kemira (Finland)
2003
There has been exponential growth in the number of membrane protein structures determined. Nevertheless, these are usually resolved absence their lipid environment. Coarse-grained molecular dynamics (CGMD) simulations enable insertion proteins into explicit models bilayers. We have automated CGMD methodology, enabling to be identified upon release PDB and embedded a membrane. The analyzed for protein-lipid interactions, identifying binding sites, revealing local bilayer deformations plus...
Abstract Purpose. This double-blind, randomized, phase III clinical trial evaluated time to progression (TTP) and overall survival in women with metastatic breast cancer (MBC) who received sialyl-TN (STn) keyhole limpet hemocyanin (KLH) vaccine. Secondary endpoints included vaccine safety immune response. Experimental design. The study population consisted of 1,028 MBC across 126 centers had previously chemotherapy either a complete or partial response no disease progression. All one-time...
Cysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step GSH synthesis is availability cysteine. However, circulating cysteine exists blood oxidised di-peptide cystine, requiring specialised transport systems for its import into cell. System xc
REV1 protein is a eukaryotic member of the Y family DNA polymerases involved in tolerance damage by replicative bypass. The precise role(s) this process not known. Here we show, using yeast two-hybrid assay and glutathione S-transferase pull-down assay, that mouse can physically interact with ubiquitin. association ubiquitin requires ubiquitin-binding motifs (UBMs) located at C terminus REV1. UBMs also mediate enhanced between monoubiquitylated PCNA In cells exposed to UV radiation,...
Selective export and retrieval of proteins between the endoplasmic reticulum (ER) Golgi apparatus is indispensable for eukaryotic cell function. An essential step in ER luminal from pH-dependent recognition a carboxyl-terminal Lys-Asp-Glu-Leu (KDEL) signal by KDEL receptor. Here, we present crystal structures chicken receptor apo state, KDEL-bound complex with an antagonistic synthetic nanobody (sybody). These show transporter-like architecture that undergoes conformational changes upon...
Amino acids play essential roles in cell biology as regulators of metabolic pathways. Arginine particular is a major signalling molecule inside the cell, being precursor for both l-ornithine and nitric oxide (NO) synthesis key regulator mTORC1 pathway. In mammals, cellular arginine availability determined by members solute carrier (SLC) 7 family cationic amino acid transporters. Whereas CAT-1 functions to supply metabolism, CAT-2A -2B are required macrophage activation important regulating...
Scientific Report10 June 2014Open Access Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters Joseph A Lyons Schools Medicine and Biochemistry & Immunology, Trinity College Dublin, Ireland Search more papers by this author Joanne L Parker Department Biochemistry, University Oxford, UK Nicolae Solcan Alette Brinth Dianfan Li Syed TA Shah Martin Caffrey Corresponding Author Simon Newstead Information Lyons1,3,‡, Parker2,‡, Solcan2, Brinth1, Li1,...
Significance The uptake of nutrients from the environment is an essential process that achieved in most cells through use secondary active transporters. POT family proton-coupled peptide transporters are one diverse nutrient systems, recognizing amino acids, peptides, nitrate, and seed-defense compounds. A long-standing question how this achieves such ligand diversity. high-resolution crystal structure combined with multiscale molecular dynamics simulations demonstrate water molecules able...
Structure of PepT2 reveals binding model for peptide recognition and enables a more rationalized approach to prodrug design.
Abstract In mammals, the kidney plays an essential role in maintaining blood homeostasis through selective uptake, retention or elimination of toxins, drugs and metabolites. Organic anion transporters (OATs) are responsible for recognition metabolites toxins nephron their eventual urinary excretion. Inhibition OATs is used therapeutically to improve drug efficacy reduce nephrotoxicity. The founding member renal organic transporter family, OAT1 (also known as SLC22A6), uses export...
Bypassing of DNA lesions by damage-tolerant polymerases depends on the interaction these enzymes with monoubiquitylated form replicative clamp protein, PCNA. We have analyzed contributions ubiquitin and PCNA binding to damage bypass damage-induced mutagenesis in Polymerase η (encoded RAD30 ) from budding yeast Saccharomyces cerevisiae . report here that a ubiquitin-binding domain provides enhanced affinity for ubiquitylated is essential vivo function polymerase, but only conjunction basal...
SUMO-targeted ubiquitin ligases (STUbLs) recognize sumoylated proteins as substrates for ubiquitylation and have been implicated in several aspects of DNA repair the damage response. However, few physiological STUbL identified, relative importance SUMO binding versus direct interactions with substrate remains a matter debate. We now present evidence that ligase Rad18 from Saccharomyces cerevisiae, which monoubiquitylates sliding clamp protein proliferating cell nuclear antigen (PCNA)...
Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition mammalian cells. PepT1 and PepT2, the proton coupled peptide transporters (POTs), function to assimilate retain diet-derived peptides play roles drug pharmacokinetics. A characteristic of POT family is mechanism selectivity, with members able recognise >8000 different peptides. In this study, we present thermodynamic evidence that bacterial transporter PepTSt, from Streptococcus...
Tuberculosis (TB) is the leading cause of death from a single infectious agent and in 2019 an estimated 10 million people worldwide contracted disease. Although treatments for TB exist, continual emergence drug-resistant variants necessitates urgent development novel antituberculars. An important new target lipid transporter MmpL3, which required construction unique cell envelope that shields Mycobacterium tuberculosis (Mtb) immune system. However, structural understanding mutations Mtb...
Abstract α‐Helical membrane proteins (MPs) are the targets for many pharmaceutical drugs and play important roles in human physiology. In recent years, significant progress has been made determining their atomic structure using X‐ray crystallography. However, a major bottleneck MP crystallography still remains, namely, identification of conditions that give crystals suitable structural determination. 2008, we undertook an analysis crystallization 121 α‐helical MPs to design rationalized...
Mammals obtain nitrogen via the uptake of di- and tri-peptides in gastrointestinal tract through action PepT1 PepT2, which are members POT family proton-coupled oligopeptide transporters. PepT2 also play an important role drug transport human body. Recent crystal structures bacterial homologs revealed a conserved peptide-binding site mechanism transport. However, key structural difference exists between mammalian with only latter containing large extracellular domain, function is currently...