A5003361772- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Amino Acid Enzymes and Metabolism
- ATP Synthase and ATPases Research
- Molecular Sensors and Ion Detection
- Neurotransmitter Receptor Influence on Behavior
- Biomedical Text Mining and Ontologies
- Semantic Web and Ontologies
- Enzyme Structure and Function
- RNA regulation and disease
- Diet and metabolism studies
- Ion Transport and Channel Regulation
- Receptor Mechanisms and Signaling
- Parasitic Infections and Diagnostics
- Neuroscience, Education and Cognitive Function
- Advanced Text Analysis Techniques
- Bacterial Genetics and Biotechnology
- Caveolin-1 and cellular processes
- Chemical Reactions and Isotopes
- Cellular transport and secretion
- Protein Interaction Studies and Fluorescence Analysis
- Porphyrin Metabolism and Disorders
- Virus-based gene therapy research
MRC Mitochondrial Biology Unit
2016-2025
Medical Research Council
2016-2025
University of Cambridge
2018-2025
Yale University
2007-2018
Wellcome Trust
2016-2018
University of Ioannina
2004-2008
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There an emphasis on selective pharmacology (where available), plus links open access knowledgebase source targets their ligands ( https://www.guidetopharmacology.org/ ), which more detailed views target ligand properties. Although constitutes...
The recent determination of the crystal structure leucine transporter from Aquifex aeolicus (aaLeuT) has provided significant insights into function neurotransmitter:sodium symporters. Transport by aaLeuT is Cl(-) independent, whereas many symporters higher organisms depend on ions. However, only ion identified in interacts with nonconserved residues extracellular loops, and thus relevance this binding site unclear. Here, we use calculations pK(A)s homology modeling to predict location a...
Serotonin transporter (SERT) is the main target for widely used antidepressant agents. Several of these drugs, including imipramine, citalopram, sertraline, and fluoxetine (Prozac), bound more avidly to SERT in presence Cl − . In contrast, did not enhance cocaine or paroxetine binding. A binding site recently identified SERT, shown be important dependent transport, was also critical dependence affinity. Mutation residues contributing this eliminated -mediated affinity increase imipramine...
Article12 April 2019Open Access Transparent process The yeast mitochondrial pyruvate carrier is a hetero-dimer in its functional state Sotiria Tavoulari Corresponding Author [email protected] orcid.org/0000-0002-4263-8905 Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK Search for more papers by this author Chancievan Thangaratnarajah Vasiliki Mavridou Michael E Harbour Jean-Claude Martinou Department Cell Biology, Geneva, Genève 4, Switzerland Edmund RS Kunji...
Abstract Mitochondrial ADP/ATP carriers import ADP into the mitochondrial matrix and export ATP to cytosol fuel cellular processes. Structures of inhibited cytoplasmic- matrix-open states have confirmed an alternating access transport mechanism, but molecular details substrate binding remain unresolved. Here, we evaluate role solvent-exposed residues translocation pathway in process binding. We identify main site, comprising three positively charged a set aliphatic aromatic residues, which...
Uptake of neurotransmitters by sodium-coupled monoamine transporters the NSS family is required for termination synaptic transmission. Transport tightly regulated protein-protein interactions involving small cytoplasmic segments at amino- and carboxy-terminal ends transporter. Although structures homologues provide information about transmembrane regions these transporters, structural arrangement terminal domains remains largely unknown. Here, we combined molecular modeling, biochemical,...
The mitochondrial pyruvate carrier (MPC) has emerged as a promising drug target for metabolic disorders, including non-alcoholic steatohepatitis and diabetes, metabolically dependent cancers neurodegenerative diseases. A range of structurally diverse small molecule inhibitors have been proposed, but the nature their interaction with MPC is not understood, composition functional human still debated. goal this study was to characterise protein in vitro, understand chemical features that...
Significance Membrane transport proteins are responsible for moving substrates, such as nutrients, vitamins, drugs, and signaling molecules across cellular membranes. A subset of these proteins, the ion-coupled transporters, use a transmembrane ion gradient to drive energetically unfavorable substrate movement from lower concentration on one side membrane higher other side. They do this by coupling ions in same or opposite direction. Coupled requires conformational changes that occur...
Prothymosin alpha (ProTalpha) is a histone H1-binding protein that interacts with the transcription coactivator CREB-binding and potentiates transcription. Based on coimmunoprecipitation mammalian two-hybrid assays, we show here ProTalpha forms complex oncoprotein SET. efficiently decondenses human sperm chromatin, while overexpression of GFP-ProTalpha in cells results global chromatin decondensation. These indicate decondensation compacted fibers an important step mechanism function.
In ion-coupled transport proteins, occupation of selective ion-binding sites is required to trigger conformational changes that lead substrate translocation. Neurotransmitter transporters, targets abused and therapeutic drugs, require Na+ Cl− for function. We recently proposed a chloride-binding site in these proteins not present Cl−-independent prokaryotic homologues. Here we describe conversion the tryptophan transporter TnaT fully functional Cl−-dependent form by single point mutation,...
Citrin, the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), is structurally and mechanistically most complex SLC25 family member, because it consists of three domains forms a homo-dimer. Each protomer has an N-terminal calcium-binding domain with EF-hands, followed by substrate-transporting C-terminal amphipathic helix. The absence or dysfunction citrin leads to deficiency, highly prevalent pan-ethnic disease. Here, we aim understand role different how they contribute pathogenic...
Search queries on biomedical databases, such as PubMed, often return a large number of results, only small subset which is relevant to the user. Ranking and categorization, can also be combined, have been proposed alleviate this information overload problem. Results categorization for databases focus work. A natural way organize citations according their MeSH annotations. comprehensive concept hierarchy used by PubMed. In paper, we present BioNav system, novel search interface that enables...
Transport proteins of the neurotransmitter sodium symporter (NSS) family regulate extracellular concentration several neurotransmitters in central nervous system. The only member this for which atomic-resolution structural data are available is prokaryotic homologue LeuT. This protein has been used as a model system to study molecular mechanism transport NSS family. In Journal Club, we discuss two strikingly different LeuT mechanisms: one involving single high-affinity substrate binding site...
Retroviral reverse transcriptase (RT) plays a definite role in retroviral life cycle and is essential for the process of retrotransposition. We investigated RNA expression endogenous transcriptases (enRTs) NIH3T3 mouse genome using, as probe, mixture RT-PCR generated products potentially detecting large number RTs following treatment with different agents. found that enRTs induced approximately 500-fold 5'-azacytidine-treatment. Amongst steroid hormones used such estradiol,...
Search queries on biomedical databases like PubMed often return a large number of results, only small subset which is relevant to the user. Ranking and categorization, can also be combined, have been proposed alleviate this information overload problem. Results categorization for focus work. A natural way organize citations according their MeSH annotations, comprehensive concept hierarchy used by PubMed. In paper, we present BioNav system, novel search interface that enables user navigate...
Gonadotrophin surge-attenuating factor (GnSAF) is an as yet unidentified ovarian that acts on the pituitary to attenuate pre-ovulatory LH surge. In a previous study, GnSAF bioactivity was proposed derive, at least in part, from C-terminal domain (95peptide) of human serum albumin (HSA).We employ here expression-secretion system Pichia pastoris produce and assay selected recombinant polypeptides HSA for activity. We show 95peptide (residues 490-585; subdomain IIIB) can be expressed P.pastoris...
Cryptosporidiumparvum is a clinically important eukaryotic parasite that causes the disease cryptosporidiosis, which manifests with gastroenteritis-like symptoms. The protist has mitosomes, are organelles of mitochondrial origin have only been partially characterized. genome encodes highly reduced set transport proteins SLC25 carrier family unknown function. Here, we studied properties one member C. parvum family, demonstrating it resembles ADP/ATP eukaryotes. However, this broader substrate...