A5038122240- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Tuberculosis Research and Epidemiology
- Amino Acid Enzymes and Metabolism
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Adenosine and Purinergic Signaling
- Wildlife-Road Interactions and Conservation
- Toxin Mechanisms and Immunotoxins
- Mycobacterium research and diagnosis
- Land Use and Ecosystem Services
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Signaling Pathways in Disease
- Protease and Inhibitor Mechanisms
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Wnt/β-catenin signaling in development and cancer
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Bacterial Genetics and Biotechnology
- Probiotics and Fermented Foods
University of Leicester
2012-2023
Institute of Structural and Molecular Biology
2018-2023
Ecological Society of America
2016-2020
John Wiley & Sons (United States)
2016-2020
Wyoming Game and Fish Department
2019
IFC Research (United Kingdom)
2018-2019
Weatherford College
1994-2016
King's College London
2012
Yancheng Institute of Technology
2012
Bergen Kommune
2012
The crystal structure of urease from Klebsiella aerogenes has been determined at 2.2 A resolution and refined to an R factor 18.2 percent. enzyme contains four structural domains: three with novel folds playing roles, (alpha beta)8 barrel domain, which the bi-nickel center. two active site nickels are 3.5 apart. One nickel ion is coordinated by ligands (with low occupancy a fourth ligand) second five ligands. carbamylated lysine provides oxygen ligand each nickel, explaining why carbon...
PD-1, a receptor expressed by T cells, B and monocytes, is potent regulator of immune responses promising therapeutic target. The structure interactions human PD-1 are, however, incompletely characterized. We present the solution nuclear magnetic resonance (NMR)-based extracellular region detailed analyses its with ligands, PD-L1 PD-L2. has typical immunoglobulin superfamily topology but differs at edge GFCC' sheet, which flexible completely lacks C" strand. Changes in backbone NMR signals...
The proteins ESAT-6 and CFP-10 have been shown to be secreted by <i>Mycobacterium tuberculosis</i> bovis</i> cells, potent T-cell antigens, a clear but as yet undefined role in tuberculosis pathogenesis. We successfully overexpressed both <i>Escherichia coli</i> developed efficient purification schemes. Under <i>in vivo</i>-like conditions, combination of fluorescence, circular dichroism, nuclear magnetic resonance spectroscopy that contains up 75% helical secondary structure, little if any...
The secreted glycoprotein sclerostin has recently emerged as a key negative regulator of Wnt signaling in bone and stimulated considerable interest potential target for therapeutics designed to treat conditions associated with low mass, such osteoporosis. We have determined the structure sclerostin, which resulted identification previously unknown binding site heparin, suggestive functional role localizing surface cells. also mapped interaction an antibody that blocks inhibition by...
LRP5 and LRP6 are proteins predicted to contain four six-bladed β-propeller domains both bind the bone-specific Wnt signaling antagonist sclerostin. Here, we report crystal structure of amino-terminal region using NMR show that ability sclerostin this molecule is mediated by central core does not involve amino- carboxyl-terminal flexible arm regions. We structured interacts with via an NXI motif (found in sequence PNAIG) within a loop (loop 2) region. This related closely previously...
Mycobacterium tuberculosis encodes five type VII secretion systems that are responsible for exporting a number of proteins, including members the Esx family, which have been linked to pathogenesis and survival within host cells. The gene cluster encoding ESX-3 is regulated by availability iron zinc, secreted protein products such as EsxG·EsxH complex associated with metal ion acquisition. EsxG EsxH previously shown form stable 1:1 heterodimeric complex, here we report solution structure...
Changes in the NMR chemical shift of backbone amide nuclei (1H and 15N) have been used to map matrix metalloproteinase (MMP) binding site on N-terminal domain tissue inhibitor metalloproteinase-2 (N-TIMP-2). Amide changes were measured formation a stable complex with catalytic stromelysin-1 (N-MMP-3). Residues significantly shifted signals mapped specifically broad covering one face molecule. This (the MMP site) consists primarily residues 1−11, 27−41, 68−73, 87−90, 97−104. The overlaps...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolution structure of the active domain tissue inhibitor metalloproteinases-2. A new member OB fold protein familyRichard A. Williamson, Gabriel Martorell, Mark D. Carr, Gillian Murphy, Andrew J. P. Docherty, Robert B. Freedman, and James FeeneyCite this: Biochemistry 1994, 33, 39, 11745–11759Publication Date (Print):October 4, 1994Publication History Published online1 May 2002Published inissue 4 October...
The high resolution structure of the N-terminal domain tissue inhibitor metalloproteinases-2 (N-TIMP-2) in solution has been determined using multidimensional heteronuclear NMR spectroscopy, with structural calculations based on an extensive set constraints, including 3132 nuclear Overhauser effect-based distance 56 hydrogen bond and 220 torsion angle constraints (an average 26.9 constraints/residue). core protein consists a five-stranded β-barrel that is homologous to found...
Ligand-induced transcription by nuclear receptors involves the recruitment of p160 coactivators such as steroid receptor coactivator 1 (SRC1), in complex with histone acetyltransferases CREB-binding protein (CBP) and p300. Here we describe solution structure a formed SRC1 interaction domain (SID) CBP activation (AD1) SRC1, both which contain four helical regions (Cα1, Cα2, Cα3, Cα3′ Sα1, Sα2′, Sα2, Sα3 SRC1). A tight four-helix bundle is between Cα1, Cα3 that capped Sα3. In contrast to AD1...
The Mycobacterium tuberculosis complex CFP-10/ESAT-6 family proteins play essential but poorly defined roles in pathogenesis. In this article we report the results of detailed spectroscopic studies several members family. This work shows that related proteins, Rv0287 and Rv0288, form a tight 1:1 complex, which is predominantly helical structure predicted to closely resemble formed by CFP-10 ESAT-6. addition, Rv0287.Rv0288 was found be significantly more stable both chemical temperature...
RNA polymerase-binding protein A (RbpA), encoded by Rv2050, is specific to the actinomycetes, where it highly conserved. In pathogen Mycobacterium tuberculosis, RbpA essential for growth and survival. binds β subunit of polymerase activates transcription unknown mechanisms, may also influence response M. tuberculosis current frontline anti-tuberculosis drug rifampicin. Here we report solution structure identify principle sigma factor σ(A) stress-induced σ(B) as interaction partners. The has...
Aiming at the design of an allosteric modulator neonatal Fc receptor (FcRn)–Immunoglobulin G (IgG) interaction, we developed a new methodology including NMR fragment screening, X-ray crystallography, and magic-angle-spinning (MAS) 100 kHz after sedimentation, exploiting very fast spinning nondeuterated soluble 42 kDa construct to obtain resolved proton-detected 2D 3D spectra. FcRn plays crucial role in regulation IgG serum albumin catabolism. It is clinically validated drug target for...
Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current and vaccines highlights importance broad cross-reactivity. This study describes deep-mining antibody repertoires hospitalized COVID-19 patients phage display technology B cell receptor (BCR) repertoire sequencing isolate neutralizing gain insights into early response. comprehensive discovery approach has yielded...
Porcine pancreatic spasmolytic polypeptide (PSP) belongs to a large family of homologous growth factor-like polypeptides characterized by disulfide-linked "trefoil motif," duplicated and conserved in various members. PSP contains two trefoil motifs, has several pharmacological actions on the gut, factor properties epithelial cells vitro. The human analogue, polypeptide, appears be involved many regenerative situations and, especially, healing gastrointestinal ulcers. One member family, pS2,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProton NMR-based determination of the secondary structure porcine pancreatic spasmolytic polypeptide: one a new family "trefoil" motif containing cell growth factorsMark D. CarrCite this: Biochemistry 1992, 31, 7, 1998–2004Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/bi00122a015https://doi.org/10.1021/bi00122a015research-articleACS...
Monoclonal antibodies have recently started to deliver on their promise as highly specific and active drugs; however, a more effective, knowledge-based approach the selection, design, optimization of potential therapeutic is currently limited by surprising lack detailed structural information for complexes formed with target proteins. Here we show that minimal antigen binding single chain variable fragments (scFv) reliably reflect all features interface present in larger Fab fragments, which...
One of the key regulatory points translation initiation is recruitment 43S preinitation complex to 5′ mRNA cap by eIF4F (eIF4A, eIF4E, and eIF4G). The tumor suppressor protein Pdcd4 has been shown inhibit cap-dependent interacting tightly with RNA helicase eIF4A via its tandem MA-3 domains. NMR studies reported here reveal a fairly extensive well defined interface between two domains in solution, which appears be stabilized network interdomain salt bridges hydrogen bonds, reveals unique...