A5059422020- Biochemical and Structural Characterization
- Ion Transport and Channel Regulation
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Transgenic Plants and Applications
- Antimicrobial Peptides and Activities
- Ion channel regulation and function
- Viral gastroenteritis research and epidemiology
- Membrane-based Ion Separation Techniques
- Pancreatic function and diabetes
- Animal Virus Infections Studies
- Advanced NMR Techniques and Applications
- Influenza Virus Research Studies
- Peptidase Inhibition and Analysis
- Enzyme Production and Characterization
- Plant Virus Research Studies
- Neonatal Respiratory Health Research
- Viral Infections and Vectors
- SARS-CoV-2 and COVID-19 Research
- Studies on Chitinases and Chitosanases
- Mitochondrial Function and Pathology
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
Nanyang Technological University
2014-2023
Peptide asparaginyl ligases (PALs) catalyze transpeptidation at the Asn residue of a short Asn-Xaa1-Xaa2 tripeptide motif. Due to their high catalytic activity toward P1-Asn substrates around neutral pH, PALs have been used extensively for peptide ligation junctions. also bind aspartyl substrates, but only when γCOOH P1-Asp remains in its neutral, protonated form, which usually requires an acidic pH. However, this limits availability amine nucleophile and, consequently, efficiency Because...
The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH has single α-helical transmembrane (TM) domain that forms pentameric ion channels. Herein, we report first inhibitor of channel, pyronin B, and have mapped its binding site to conserved surface RSV pentamer, at C-terminal end domain. validity structural model used been confirmed using bicellar membrane-mimicking environment. However, in bicelles stretch TM extends up...
It has been shown previously in the severe acute respiratory syndrome coronavirus (SARS-CoV) that two point mutations, N15A and V25F, transmembrane domain (TMD) of envelope (E) protein abolished channel activity led to
Background: Protein theranostics integrate both diagnostic and treatment functions on a single diseasetargeting protein.However, the preparation of these multimodal agents remains major challenge.Ideally, conventional recombinant proteins should be used as starting materials for modification with desired detection therapeutic functionalities, but simple chemical strategies that allow introduction two different modifications into protein in site-specific manner are not currently available.We...
The recently discovered peptide asparaginyl ligases (PALs) from cyclotide-producing plants are efficient and versatile tools for protein engineering. Here, we report immobilization of two glycosylated PALs, butelase-1 VyPAL2, using three different attachment methods their applications We compared indirectly via noncovalent affinity capture NeutrAvidin or concanavalin A agarose beads directly covalent coupling free amines on the enzyme surface with N-hydroxysuccinimide (NHS) ester attached...
Butelase-1, an asparaginyl endopeptidase or legumain, is the prototypical and fastest known Asn/Asp-specific peptide ligase. It highly useful for engineering macrocyclization of peptides proteins. However, certain biochemical properties applications naturally occurring recombinant butelase-1 remain unexplored. Here we report methods to increase yield natural bacterial expressed how they can be used improve stability activity two important industrial enzymes, lipase phytase, by end-to-end...
Recently, we have successfully developed a 1020-MHz (24.0 T) NMR system. The magnet consists of superconducting coils having low critical temperature and high temperature. It was confi...
Lipoyl(Octanoyl) Transferase 2 (LIPT2) is a protein involved in the post-translational modification of key energy metabolism enzymes humans. Defects lipoic acid synthesis and transfer start to emerge as causes fatal or severe early-onset disease. We show that first 31 amino acids N-terminus LIPT2 represent mitochondrial targeting sequence inhibition transit mitochondrion results apoptotic cell death associated with activation volume decrease (AVD) current normotonic conditions, well...
Legumains, also known as asparaginyl endopeptidases (AEPs), cleave peptide bonds after Asn/Asp (Asx) residues. In plants, certain legumains have ligase activity that catalyzes biosynthesis of Asx-containing cyclic peptides. An example is the MCoTI-I/II, a squash family-derived trypsin inhibitor, which involves splicing to remove N-terminal prodomain and then N-to-C-terminal cyclization mature domain. To identify plant responsible for maturation these peptides, we isolated characterized...
The nonstructural (NS) protein NS4A in flaviviruses is a membrane that critical for virulence, and, among other roles, it participates morphogenesis. In dengue virus (DENV), the hydrophilic N–terminal tail, together with first transmembrane domain, involved both homo-oligomerization and hetero–oligomerization NS4B. DENV Zika (ZIKV), this N-terminal tail (residues 1–48) forms random coil solution but becomes mostly α-helical upon interaction detergents or lipid membranes. Herein, we show...
Abstract Peptidyl asparaginyl ligases (PALs) are powerful tools for peptide macrocyclization. Herein, we report that a derivative of Asn, namely N γ ‐hydroxyasparagine or Asn(OH), is an unnatural P1 substrate PALs. By Asn(OH)‐mediated cyclization, prepared cyclic peptides as new matrix metalloproteinase 2 (MMP2) inhibitors displaying the hydroxamic acid moiety Asn(OH) key pharmacophore. The most potent ( K i =2.8±0.5 nM) was built on hyperstable tetracyclic scaffold rhesus theta defensin‐1....
Grafting a bioactive peptide onto disulfide-rich scaffold is promising approach to improve its structure and metabolic stability. The ginkgo plant-derived β-ginkgotide β-gB1 highly unusual molecule: Small, hyperdisulfide, found only in selected ancient plants. It also contains conserved 16-amino-acid core with three interlocking disulfides, as well six-amino-acid inter-cysteine loop 2 suitable for grafting epitopes. However, very little known about this recently-discovered family of...
Aquaporins (AQPs) are membrane proteins that enable water transport across cellular plasma membranes in response to osmotic gradients. Phenotypic analyses have revealed important physiological roles for AQPs, and the potential AQP channel modulators various disease states has been proposed. For example, AQP1 is overexpressed tumor microvessels, this correlates with higher metastatic aggressiveness of malignancy. Chemical would help identifying precise contribution activity these states....
Dendrimeric and branched peptides are polypeptides formed by diverse types of scaffolds to give them different forms. Previously, we reported a cascade-type, Lys-scaffolded antimicrobial peptide dendrimer D4R tethered with four RLYR tetrapeptides. Antimicrobial is broad-spectrum, salt insensitive, as potent the natural-occurring tachyplesins, displaying minimum inhibitory concentrations (MIC) < 1 μM. However, relationships between potency remain undefined. Here, report design novel...
Abstract Peptidyl asparaginyl ligases (PALs) are powerful tools for peptide macrocyclization. Herein, we report that a derivative of Asn, namely N γ ‐hydroxyasparagine or Asn(OH), is an unnatural P1 substrate PALs. By Asn(OH)‐mediated cyclization, prepared cyclic peptides as new matrix metalloproteinase 2 (MMP2) inhibitors displaying the hydroxamic acid moiety Asn(OH) key pharmacophore. The most potent ( K i =2.8±0.5 nM) was built on hyperstable tetracyclic scaffold rhesus theta defensin‐1....