A5001179088- Microbial Metabolic Engineering and Bioproduction
- Biochemical Acid Research Studies
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Enzyme Catalysis and Immobilization
- Metabolism and Genetic Disorders
- Parkinson's Disease Mechanisms and Treatments
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Hippo pathway signaling and YAP/TAZ
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Amino Acid Enzymes and Metabolism
- Signaling Pathways in Disease
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- Histone Deacetylase Inhibitors Research
- Alcoholism and Thiamine Deficiency
- Viral gastroenteritis research and epidemiology
- Protein Structure and Dynamics
- Escherichia coli research studies
- Genomics and Chromatin Dynamics
Inserm
2019
Center for Infection and Immunity of Lille
2019
University College London
2007-2018
The Francis Crick Institute
2016
MRC Protein Phosphorylation and Ubiquitylation Unit
2015
University of Dundee
2015
Institute of Structural and Molecular Biology
2014-2015
Cancer Research UK
2012-2014
The Honourable Society of Lincoln's Inn
2013
Institute of Cancer Research
2012
Scientific Report26 June 2015Open Access Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation Agne Kazlauskaite MRC Protein Phosphorylation Ubiquitylation Unit, College of Life Sciences, University Dundee, UK Search more papers by this author R Julio Martínez-Torres Scott Wilkie Division Biological Chemistry Drug Discovery, Atul Kumar Julien Peltier Alba Gonzalez Clare Johnson Jinwei Zhang Anthony G Hope Mark Peggie Matthias...
Abstract The PARK 2 gene is mutated in 50% of autosomal recessive juvenile parkinsonism ( ARJP ) cases. It encodes parkin, an E3 ubiquitin ligase the RBR family. Parkin exists autoinhibited state that activated by phosphorylation its N‐terminal ubiquitin‐like (Ubl) domain and binding phosphoubiquitin. We describe 1.8 Å crystal structure human parkin fully inhibited identify key interfaces to maintain inhibition. phosphoubiquitin‐binding interface, provide a model for phosphoubiquitin–parkin...
Mutations in the park2 gene, encoding RING-inBetweenRING-RING E3 ubiquitin ligase parkin, cause 50% of autosomal recessive juvenile Parkinsonism cases. More than 70 known pathogenic mutations occur throughout many which cluster inhibitory amino-terminal ubiquitin-like domain, and carboxy-terminal RING2 domain that is indispensable for transfer. A structural rationale showing how alter parkin function still lacking. Here we show structure distinct from canonical RING ligases lacks key...
Abstract Effective application of whole-cell devices in synthetic biology and biocatalysis will always require consideration the uptake molecules interest into cell. Here we demonstrate that AlkL protein from Pseudomonas putida GPo1 is an alkane import capable industrially relevant rates C 7 -C 16 n-alkanes. Without alkL expression, native E.coli n-alkane was rate-limiting step both bioconversion n-alkanes activation a biosensor by 10 11 alkanes. By coexpression as transporter plug-in,...
During the last decade use of transaminases for production pharmaceutical and fine chemical intermediates has attracted a great deal attention. Transaminases are versatile biocatalysts efficient amine many have (S)-enantiospecificity. with (R)-specificity needed to expand applications these enzymes in biocatalysis. In this work we identified fungal putative (R)-specific transaminase from Eurotiomycetes Nectria haematococca, cloned synthetic version gene, demonstrated (R)-selective...
Highlights•Kinetics of RET autophosphorylation identify early and late sites•Evidence for a kinase domain cis-inhibitory tether is presented•Oncogenic subverts cis-inhibition perturbs the trajectory•Oncogenic overactive better trans-autophosphorylation substrateSummaryTo decipher molecular basis activation oncogenic deregulation, we defined temporal sequence by label-free quantitative mass spectrometry. Early sites map to regions flanking core, while within loop only form at later time...
Mutations in the nucleotide-binding oligomerization domain protein 12 (NLRP12) cause recurrent episodes of serosal inflammation. Here we show that NLRP12 efficiently sequesters HSP90 and promotes K48-linked ubiquitination degradation NOD2 response to bacterial muramyl dipeptide (MDP). This interaction is mediated by linker-region proximal NLRP12. Consequently, disease-causing R284X mutation fails repress MDP-induced NF-κB subsequent activity JAK/STAT signaling pathway. While deficiency...
Chiral amino alcohols are structural motifs present in sphingolipids, antibiotics, and antiviral glycosidase inhibitors. Their chemical synthesis presents several challenges establishing at least two chiral centres. Here a de novo metabolic pathway using transketolase enzyme coupled with transaminase has been assembled. To synthesise this motif one of the strategies to obtain high conversions from transaminase/transketolase cascade is use hydroxypyruvate (HPA) as two-carbon donor for...
Receptor tyrosine kinases exhibit a variety of activation mechanisms despite highly homologous catalytic domains. Such diversity arises through coupling extracellular ligand-binding portions with variable intracellular sequences flanking the kinase domain and specific patterns autophosphorylation sites. Here, we show that juxtamembrane (JM) segment enhances RET activity Y687. This phospho-site is also required by JM region to rescue an otherwise catalytically deficient activation-loop mutant...
Abstract We have previously developed a rapid microplate‐based approach for measuring the denaturation curves by intrinsic tryptophan fluorescence simple monomeric and two‐state unfolding proteins. Here we demonstrate that it can accurately resolve multiple conformational transitions occur during of complex multimeric cofactor associated protein. also analyzed effect two active‐site mutations, D381A Y440A upon pathway transketolase using measurements, compare results from classical...