A5008719558- Enzyme Structure and Function
- Viral-associated cancers and disorders
- Cytomegalovirus and herpesvirus research
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Poxvirus research and outbreaks
- Bacteriophages and microbial interactions
- Virus-based gene therapy research
- Nanopore and Nanochannel Transport Studies
- Herpesvirus Infections and Treatments
- Polyomavirus and related diseases
- Histiocytic Disorders and Treatments
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Atherosclerosis and Cardiovascular Diseases
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- HIV/AIDS drug development and treatment
- Signaling Pathways in Disease
- Parvovirus B19 Infection Studies
- Electrostatics and Colloid Interactions
Universidade Nova de Lisboa
2009-2021
Instituto Português Da Qualidade
2017
Queen's University
2009
Instituto de Biologia Experimental e Tecnológica
2009
National Yang Ming Chiao Tung University
2009
Imperial College London
2004-2007
Division of Chemistry
2006
University of York
1997-2003
Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators innate immune signalling. VACV protein N1 is an intracellular homodimer that contributes to virulence was reported inhibit nuclear factor (NF)- κ B However, analysis NF- signalling in cells infected with recombinant viruses or without the N1L gene showed no difference B-dependent expression. Given promotes virulence, other possible functions were investigated this revealed inhibitor...
Latency-associated nuclear antigen (LANA) mediates γ2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 Å resolution. The reveals an alpha-beta fold that assembles as a dimer, reminiscent Epstein-Barr virus EBNA1. A predicted DNA binding surface is present opposite this interface positive electrostatic patch. Targeted recognition substitutions eliminated binding, while certain charged...
Gold nanoparticles are widely used in various applications fields including chemistry, engineering, biology, medicine, and electronics. These materials can be synthesized modified with ligands containing different functional groups. Among nanoparticles' characteristics, chemical surface composition is likely to a crucial feature, demanding robust analytical methodologies for its assessment. Single molecule analysis using the biological nanopores α-hemolysin E111A mutant presented here as...
Many pathogens, including Kaposi's sarcoma herpesvirus (KSHV), lack tractable small animal models. KSHV persists as a multi-copy, nuclear episome in latently infected cells. latency-associated antigen (kLANA) binds viral terminal repeat (kTR) DNA to mediate persistence. Model pathogen murine gammaherpesvirus 68 (MHV68) mLANA acts analogously on mTR DNA. kLANA and differ substantially size kTR show little sequence conservation. Here, we find act reciprocally persistence of TR Further, rescued...
Poxviruses express numerous proteins involved in manipulating the host immune response. Analysis of primary sequence and predicted structure 134R protein Yaba-like disease virus (Y134R) indicated that it is similar to cellular IL-10 family, specifically IL-19, IL-20 IL-24. A flag-tagged Y134R was expressed from mammalian cells identified as a secreted, monomeric glycoprotein stimulated signal transduction class II cytokine receptors IL-20R α /IL-20R β (IL-20R type1) IL-22R/IL-20R type 2)....
Latency-associated nuclear antigen (LANA) is central to episomal tethering, replication and transcriptional regulation of γ2-herpesviruses. LANA binds cooperatively the terminal repeat (TR) region viral episome via adjacent binding sites (LBS), but molecular mechanism by which assembles on TR remains elusive. We show that KSHV MHV-68 proteins bind LBS DNA using strikingly different modes. Solution structure complexes revealed while kLANA tetramer intrinsically bent both in free bound state...
Single channel recordings were used to determine the effect of direct electrostatic interactions between sulfonate-coated gold nanoparticles and constriction Staphylococcus aureus α-hemolysin protein on ionic current amplitude. We provide evidence that Lys147 can interact with sulfonate groups at nanoparticle surface, these reversibly block 100% residual current. is normally involved in a salt bridge Glu111. The capture leads partial neutral pH values, but protonation Glu111 2.8 results full...
We present the first study of a novel, more sensitive method for characterization nanoparticles (NPs). This approach combines detection via protein nanopore with modification its interaction behavior using molecular adaptor. identify different populations 3-mercapto-1-propanesulfonate (MPSA)-modified-gold NPs biological nanopores α-hemolysin (αHL) and M113N mutant equipped noncovalently bound γ-cyclodextrin molecule as stochastic sensor. Identification takes place on basis extent current...
Two mutant forms of penicillin acylase from Escherichia coli strains, selected using directed evolution for the ability to use glutaryl-l-leucine growth [Forney, Wong and Ferber (1989) Appl. Environ. Microbiol. 55, 2550—2555], are changed within one codon, replacing B-chain residue PheB71 with either Cys or Leu. Increases up a factor ten in kcat/Km values substrates possessing phenylacetyl leaving group consistent decrease Ks. Values increased at least 100-fold. A CysB71 pH is binding...
Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome decorated with epigenetic marks. Here, we show that latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive terminal repeat elements during primary infection. LANA interacts complex members, including WDR5, integrates into...
The latency-associated nuclear antigen from Kaposi's sarcoma-associated herpesvirus (KSHV), kLANA, and its homolog the murid 4 (MuHV-4), mLANA, are essential for viral latency. kLANA is nearly four times size of mainly due to an extensive central repeat region that absent in mLANA. Both proteins harbor a C-terminal DNA binding domain (DBD). DBD binds terminal (TR) sequences genome mediate persistence. Despite structural conservation, mLANA DBDs differ sequence mode oligomerization. oligomers...
Uracil-DNA N -glycosylase (UNG) is a DNA-repair enzyme in the base-excision repair (BER) pathway which removes uracil from DNA. Here, crystal structure of UNG extremophilic bacterium Deinococcus radiodurans ( Dr UNG) complex with DNA reported at resolution 1.35 Å. Prior to crystallization experiments, affinity between and different oligonucleotides was tested by electrophoretic mobility shift assays (EMSAs). As result this analysis, two 16 nt double-stranded DNAs were chosen for...
RNA degradation is important in the post-transcriptional control of gene expression. The processing, and quality performed by many different classes ribonucleases. Ribonuclease II (RNase II) a 643-amino-acid enzyme that degrades single-stranded from its 3′-end, releasing ribonucleoside 5′-monophosphates. RNase was expressed both as wild type D209N mutant form. latter also produced an SeMet derivative. various protein forms were crystallized using vapour-diffusion method. Wild-type two...
ABSTRACT Viruses have evolved mechanisms to hijack components of cellular E3 ubiquitin ligases, thus modulating the ubiquitination pathway. However, biological relevance such for viral pathogenesis in vivo remains largely unknown. Here, we utilized murid herpesvirus 4 (MuHV-4) infection mice as a model system address role MuHV-4 latency-associated nuclear antigen (mLANA) ligase activity gammaherpesvirus latent infection. We show that specific mutations mLANA SOCS box (V199A, V199A/L202A, or...
Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes latently infected cells. LANA DNA replication and segregates to progeny nuclei. The structure the binding domain was recently solved, revealing positive electrostatic patch opposite surface, which is site BET protein binding. Here we investigate functional LANA-mediated episome persistence. As expected, mutants...
A new crystal form of penicillin acylase (penicillin amidohydrolase, E.C. 3.5.1.11) from Escherichia coli W (ATCC 11105) is reported. The crystals were grown using a combination hanging-drop and streak-seeding methods. are in the monoclinic space group P2(1) with cell dimensions = 51.52, b 131.95, c 64.43 A, beta 106.12 degrees. There one heterodimer asymmetric unit (V(m) 2.45 A(3) Da(-1)) solvent content 49%. Preliminary data have been collected to d(min) 2.7 MAR Research image plate...