Search results for: Alan J. Robinson

Items from 1 to 20 out of 21 results

article

Proximal Cysteines that Enhance Lysine N-Acetylation of Cytosolic Proteins in Mice Are Less Conserved in Longer-Living Species

Andrew M. James, Anthony C. Smith, Cassandra L. Smith, Alan J. Robinson, more

Cell Reports > 2018 > 24 > 6 > 1445-1455

Acetyl-coenzyme A (CoA) is an abundant metabolite that can also alter protein function through non-enzymatic N-acetylation of protein lysines. This N-acetylation is greatly enhanced in vitro if an adjacent cysteine undergoes initial S-acetylation, as this can lead to S→N transfer of the acetyl moiety. Here, using modeled mouse structures of 619 proteins N-acetylated in mouse liver, we show lysine...

article

MitoCore: a curated constraint-based model for simulating human central metabolism

Anthony C. Smith, Filmon Eyassu, Jean-Pierre Mazat, Alan J. Robinson

BMC Systems Biology > 2017 > 11 > 1 > 1-13

Background The complexity of metabolic networks can make the origin and impact of changes in central metabolism occurring during diseases difficult to understand. Computer simulations can help unravel this complexity, and progress has advanced in genome-scale metabolic models. However, many models produce unrealistic results when challenged to simulate abnormal metabolism as they include incorrect...

article

Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling

Łukasz P Zieliński, Anthony C Smith, Alexander G Smith, Alan J Robinson

Mitochondrion > 2016 > 31 > C > 45-55

Mitochondrial respiratory chain dysfunction causes a variety of life-threatening diseases affecting about 1 in 4300 adults. These diseases are genetically heterogeneous, but have the same outcome; reduced activity of mitochondrial respiratory chain complexes causing decreased ATP production and potentially toxic accumulation of metabolites. Severity and tissue specificity of these effects varies between...

article

Mutations in FBXL4, Encoding a Mitochondrial Protein, Cause Early-Onset Mitochondrial Encephalomyopathy

Xiaowu Gai, Daniele Ghezzi, Mark A. Johnson, Caroline A. Biagosch, more

The American Journal of Human Genetics > 2013 > 93 > 3 > 482-495

Whole-exome sequencing and autozygosity mapping studies, independently performed in subjects with defective combined mitochondrial OXPHOS-enzyme deficiencies, identified a total of nine disease-segregating FBXL4 mutations in seven unrelated mitochondrial disease families, composed of six singletons and three siblings. All subjects manifested early-onset lactic acidemia, hypotonia, and developmental...

article

Mitochondrial carrier homolog 2 (MTCH2): The recruitment and evolution of a mitochondrial carrier protein to a critical player in apoptosis

Alan J. Robinson, Edmund R.S. Kunji, Atan Gross

Experimental Cell Research > 2012 > 318 > 11 > 1316-1323

Recent studies report mitochondrial carrier homolog 2 (MTCH2) as a novel and uncharacterized protein that acts as a receptor-like protein for the truncated BH3-interacting domain death agonist (tBID) protein in the outer membrane of mitochondria. These studies, using mouse embryonic stem cells and fibroblasts as well as mice with a conditional knockout of MTCH2 in the liver, showed that deletion of...

article

Fumarate Is Cardioprotective via Activation of the Nrf2 Antioxidant Pathway

Houman Ashrafian, Gabor Czibik, Mohamed Bellahcene, Dunja Aksentijević, more

Cell Metabolism > 2012 > 15 > 3 > 361-371

The citric acid cycle (CAC) metabolite fumarate has been proposed to be cardioprotective; however, its mechanisms of action remain to be determined. To augment cardiac fumarate levels and to assess fumarate's cardioprotective properties, we generated fumarate hydratase (Fh1) cardiac knockout (KO) mice. These fumarate-replete hearts were robustly protected from ischemia-reperfusion injury (I/R). To...

article

Arabidopsis calcium-binding mitochondrial carrier proteins as potential facilitators of mitochondrial ATP-import and plastid SAM-import

Simon Stael, Agostinho G. Rocha, Alan J. Robinson, Przemyslaw Kmiecik, more

FEBS Letters > 2011 > 585 > 24 > 3935-3940

Chloroplasts and mitochondria are central to crucial cellular processes in plants and contribute to a whole range of metabolic pathways. The use of calcium ions as a secondary messenger in and around organelles is increasingly appreciated as an important mediator of plant cell signaling, enabling plants to develop or to acclimatize to changing environmental conditions. Here, we have studied the four...

article

The Fasted/Fed Mouse Metabolic Acetylome: N6-Acetylation Differences Suggest Acetylation Coordinates Organ-Specific Fuel Switching

Li Yang, Bhavapriya Vaitheesvaran, Kirsten Hartil, Alan J. Robinson, more

Journal of Proteome Research > 2011 > 10 > 9 > 4134 - 4149

article

Functional and structural role of amino acid residues in the matrix α-helices, termini and cytosolic loops of the bovine mitochondrial oxoglutarate carrier

Daniela V. Miniero, Anna R. Cappello, Rosita Curcio, Anna Ludovico, more

BBA - Bioenergetics > 2011 > 1807 > 3 > 302-310

The mitochondrial oxoglutarate carrier belongs to the mitochondrial carrier family and exchanges oxoglutarate for malate and other dicarboxylates across the mitochondrial inner membrane. Here, single-cysteine mutant carriers were engineered for every residue in the amino- and carboxy-terminus, cytoplasmic loops, and matrix α-helices and their transport activity was measured in the presence and absence...

article

A metabolic model of the mitochondrion and its use in modelling diseases of the tricarboxylic acid cycle

Anthony C Smith, Alan J Robinson

BMC Systems Biology > 2011 > 5 > 1 > 1-13

Background Mitochondria are a vital component of eukaryotic cells and their dysfunction is implicated in a large number of metabolic, degenerative and age-related human diseases. The mechanism or these disorders can be difficult to elucidate due to the inherent complexity of mitochondrial metabolism. To understand how mitochondrial metabolic dysfunction contributes to these diseases, a metabolic model...

article

A Simple and Effective Co‐Catalyst for Ring‐Closing Enyne Metathesis Using Grubbs I type Catalysts: A Practical Alternative to “Mori’s Conditions”

Guy C. Lloyd‐Jones, Alan J. Robinson, Laurent Lefort, Johannes G. de Vries

Chemistry – A European Journal > 16 > 31 > 9449 - 9452

“Catch‐and‐release”: Simple alk‐1‐enes are effective at liberating buta‐1,3‐dienes from vinyl alkylidene ruthenium complexes, as well as undergoing alkene–alkylidene exchange with enyne substrates to regenerate the alk‐1‐ene. This ability to “catch‐and‐release” ruthenium alkylidenes allows alk‐1‐enes higher than ethylene (“Mori's conditions”) to be used as a co‐catalysts in terminal enyne metathesis...

article

Coupling of proton and substrate translocation in the transport cycle of mitochondrial carriers

Edmund RS Kunji, Alan J Robinson

Current Opinion in Structural Biology > 2010 > 20 > 4 > 440-447

Members of the mitochondrial carrier family are involved in transporting keto acids, amino acids, nucleotides, inorganic ions and co-factors across the mitochondrial inner membrane. The transporters are thought to share the same structural fold, which consists of six trans-membrane α-helices and three matrix helices, arranged with threefold pseudo-symmetry. During the transport cycle two salt bridge...

article

The transport mechanism of mitochondrial carriers based on the analysis of pseudo-symmetry

Edmund R.S. Kunji, Alan J. Robinson

BBA - Bioenergetics > 2010 > 1797 > Supplement > 41-42

article

Establishing the role of the mitochondrial carrier MTCH2

Atan Gross, Alan J. Robinson, Edmund R.S. Kunji

BBA - Bioenergetics > 2010 > 1797 > Supplement > 44

article

S3/4 Substrate recognition and transport mechanism of mitochondrial carriers

Edmund R.S. Kunji, Alan J. Robinson

BBA - Bioenergetics > 2008 > 1777 > Supplement > S25

article

Functional and Structural Role of Amino Acid Residues in the Odd-numbered Transmembrane α-Helices of the Bovine Mitochondrial Oxoglutarate Carrier

Anna R. Cappello, Daniela V. Miniero, Rosita Curcio, Anna Ludovico, more

Journal of Molecular Biology > 2007 > 369 > 2 > 400-412

The mitochondrial oxoglutarate carrier (OGC) plays an important role in the malate-aspartate shuttle, the oxoglutarate-isocitrate shuttle and gluconeogenesis. To establish amino acid residues that are important for function, each residue in the transmembrane α-helices H1, H3 and H5 was replaced systematically by a cysteine in a fully functional mutant carrier that was devoid of cysteine residues....

article

Functional and Structural Role of Amino Acid Residues in the Even-numbered Transmembrane α-Helices of the Bovine Mitochondrial Oxoglutarate Carrier

Anna Rita Cappello, Rosita Curcio, Daniela Valeria Miniero, Italo Stipani, more

Journal of Molecular Biology > 2006 > 363 > 1 > 51-62

The mitochondrial oxoglutarate carrier exchanges cytosolic malate for 2-oxoglutarate from the mitochondrial matrix. Orthologs of the carrier have a high degree of amino acid sequence conservation, meaning that it is impossible to identify residues important for function on the basis of this criterion alone. Therefore, each amino acid residue in the transmembrane α-helices H2 and H6 was replaced by...

article

The conserved substrate binding site of mitochondrial carriers

Edmund R.S. Kunji, Alan J. Robinson

BBA - Bioenergetics > 2006 > 1757 > 9-10 > 1237-1248

Mitochondrial carriers transport nucleotides, co-factors and metabolic intermediates across the inner mitochondrial membrane permeability barrier. They belong to a family of transporters unique to eukaryotes and they differ in structure and transport mechanism from other secondary transporters. The main structural fold consists of a barrel of six transmembrane α-helices closed at the matrix side by...

article

Synergy between combinatorial chemistry and de novo design

Andrew R. Leach, Richard A. Bryce, Alan J. Robinson

Journal of Molecular Graphics and Modelling > 2000 > 18 > 4-5 > 526

article

Synergy between combinatorial chemistry and de novo design2 2 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom.

Andrew R Leach, Richard A Bryce, Alan J Robinson

Journal of Molecular Graphics and Modelling > 2000 > 18 > 4-5 > 358-367

Traditional de novo design algorithms are able to generate many thousands of ligand structures that meet the constraints of a protein structure, but these structures are often not synthetically tractable. In this article, we describe how concepts from structure-based de novo design can be used to explore the search space in library design. A key feature of the approach is the requirement that specific...

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INFONA - science communication portal

Search results for: Alan J. Robinson

Proximal Cysteines that Enhance Lysine N-Acetylation of Cytosolic Proteins in Mice Are Less Conserved in Longer-Living Species

MitoCore: a curated constraint-based model for simulating human central metabolism

Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling

Mutations in FBXL4, Encoding a Mitochondrial Protein, Cause Early-Onset Mitochondrial Encephalomyopathy

Mitochondrial carrier homolog 2 (MTCH2): The recruitment and evolution of a mitochondrial carrier protein to a critical player in apoptosis

Fumarate Is Cardioprotective via Activation of the Nrf2 Antioxidant Pathway

Arabidopsis calcium-binding mitochondrial carrier proteins as potential facilitators of mitochondrial ATP-import and plastid SAM-import

The Fasted/Fed Mouse Metabolic Acetylome: N6-Acetylation Differences Suggest Acetylation Coordinates Organ-Specific Fuel Switching

Functional and structural role of amino acid residues in the matrix α-helices, termini and cytosolic loops of the bovine mitochondrial oxoglutarate carrier

A metabolic model of the mitochondrion and its use in modelling diseases of the tricarboxylic acid cycle

A Simple and Effective Co‐Catalyst for Ring‐Closing Enyne Metathesis Using Grubbs I type Catalysts: A Practical Alternative to “Mori’s Conditions”

Coupling of proton and substrate translocation in the transport cycle of mitochondrial carriers

The transport mechanism of mitochondrial carriers based on the analysis of pseudo-symmetry

Establishing the role of the mitochondrial carrier MTCH2

S3/4 Substrate recognition and transport mechanism of mitochondrial carriers

Functional and Structural Role of Amino Acid Residues in the Odd-numbered Transmembrane α-Helices of the Bovine Mitochondrial Oxoglutarate Carrier

Functional and Structural Role of Amino Acid Residues in the Even-numbered Transmembrane α-Helices of the Bovine Mitochondrial Oxoglutarate Carrier

The conserved substrate binding site of mitochondrial carriers

Synergy between combinatorial chemistry and de novo design

Synergy between combinatorial chemistry and de novo design2 2 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom.

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