A5061136777- Invertebrate Immune Response Mechanisms
- Bone Metabolism and Diseases
- Protease and Inhibitor Mechanisms
- Antimicrobial Peptides and Activities
- Venomous Animal Envenomation and Studies
- Electrocatalysts for Energy Conversion
- Microtubule and mitosis dynamics
- Enzyme Production and Characterization
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
- Plant Molecular Biology Research
- Parasitic Infections and Diagnostics
- Peptidase Inhibition and Analysis
- Fungal and yeast genetics research
- Insect Resistance and Genetics
- Enzyme function and inhibition
- Metalloenzymes and iron-sulfur proteins
- Cell Adhesion Molecules Research
- Enzyme Structure and Function
- Calpain Protease Function and Regulation
- Antibiotic Resistance in Bacteria
- Mass Spectrometry Techniques and Applications
- Genomics and Chromatin Dynamics
- Natural product bioactivities and synthesis
National University of Singapore
2008-2020
University of Liverpool
2019
University of Cambridge
2015
University of Warwick
2013
Institute of Molecular and Cell Biology
2010
Biotechnology Research Institute
2008
National Research Council Canada
2008
McGill University
2008
Abstract Sgm (Sisomicin-gentamicin methyltransferase) from antibiotic-producing bacterium Micromonospora zionensis is an enzyme that confers resistance to aminoglycosides like gentamicin and sisomicin by specifically methylating G1405 in bacterial 16S rRNA. belongs the aminoglycoside methyltransferase (Arm) family of enzymes have been recently found spread horizontal gene transfer among disease-causing bacteria. Structural characterization Arm key understand their mechanism action develop...
ABSTRACT Microtubules execute diverse mitotic events that are spatially and temporally separated; the underlying regulation is poorly understood. By combining drug treatments, large-scale immunoprecipitation mass spectrometry, we report first comprehensive map of phase-specific protein interactions microtubule-end binding protein, EB1. EB1 interacts with some, but not all, its partners throughout mitosis. We show interaction Astrin-SKAP complex, a key regulator chromosome segregation,...
Copper-containing nitrite reductases (CuNiRs) that convert NO
Sexually reproducing organisms halve their cellular ploidy during gametogenesis by undergoing a specialized form of cell division known as meiosis. During meiosis, single round DNA replication is followed two rounds nuclear divisions (referred to meiosis I and II). While sister kinetochores bind microtubules emanating from opposite spindle poles mitosis, they originating the same pole I. This phenomenon referred mono-orientation essential for setting up reductional mode chromosome...
We report a series of noncovalent, reversible inhibitors cathepsin L that have been designed to explore additional binding interactions with the S′ subsites. The design was based on our previously reported crystal structure suggested possibility engineering increased subsites ((Chowdhury et al. J. Med. Chem. 2002, 45, 5321−5329)). A representative these new has co-crystallized mature L, and solved refined at 2.2 Å. described in this work extend farther into cathepsins than any literature...
It is generally assumed that tethering enhances rates of electron harvesting and delivery to active sites in multidomain enzymes by proximity sampling mechanisms. Here, we explore this idea a tethered 3-domain, trimeric copper-containing nitrite reductase. By reverse engineering, find does not enhance the rate from its pendant cytochrome c catalytic core. Using linker harbors gatekeeper tyrosine access channel, haem domain enables catalysis other Tethering communicates redox state distant...
Serine proteases play a crucial role in host-pathogen interactions. In the innate immune system of invertebrates, multi-domain protease inhibitors are important for regulation interactions and antimicrobial activities. inhibitors, 9.3-kDa CrSPI isoforms 1 2, have been identified from hepatopancreas horseshoe crab, Carcinoscorpius rotundicauda. The CrSPIs were biochemically active, especially CrSPI-1, which potently inhibited subtilisin (Ki = 1.43 nM). has grouped with non-classical...
We report the crystal structures of three noncovalent retrobinding inhibitors in complex with mature cathepsin L up to resolutions 2.5, 1.8, and 2.5 Å, respectively. These were Bpa-(Nε-Bpa)Lys-DArg-Tyr-Npe, Bpa-(Nε-Bpa)Lys-DArg-Phe-Npe, Bpa-MCys-DArg-Phe-Npe, where Bpa = biphenylacetyl Pea N-phenylethyl. selected clarify binding mode biphenyl groups S′ subsites because addition a second does not improve potency. Examination symmetry-related monomers revealed inhibitor−inhibitor packing...
Protease inhibitors play a decisive role in maintaining homeostasis and eliciting antimicrobial activities. Invertebrates like the horseshoe crab have developed unique modalities with serine protease to detect respond microbial host proteases. Two isoforms of an immunomodulatory two-domain Kazal-like inhibitor, CrSPI-1 CrSPI-2, been recently identified hepatopancreas crab, Carcinoscorpius rotundicauda. Full length domain 2 display powerful inhibitory activities against subtilisin. However,...
Serine proteases play a major role in host–pathogen interactions. The innate immune system is known to respond invading pathogens nonspecific manner. serine protease cascade an essential component of the horseshoe crab. inhibitor CrSPI isoform 1 (CrSPI-1), unique nonclassical Kazal-type molecular weight 9.3 kDa, was identified from hepatopancreas crab Carcinoscorpius rotundicauda. It potently inhibits subtilisin and constitutes powerful defence against microbes. Here, cloning, expression,...