A5072382036- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Ion Channels and Receptors
- Toxin Mechanisms and Immunotoxins
- Neurobiology and Insect Physiology Research
- Bacterial Genetics and Biotechnology
- Yersinia bacterium, plague, ectoparasites research
- Insect and Pesticide Research
- Insect Resistance and Genetics
- Caveolin-1 and cellular processes
- Nicotinic Acetylcholine Receptors Study
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Phosphodiesterase function and regulation
- S100 Proteins and Annexins
- Phytochemical Studies and Bioactivities
- Computational Drug Discovery Methods
Weatherford College
2024
Boehringer Ingelheim (Australia)
2024
The University of Queensland
2015-2024
Central Queensland University
2024
Significance Six million people die each year from stroke, and 5 survivors are left with a permanent disability. Moreover, the neuronal damage caused by stroke often triggers progressive decline in cognitive function that doubles risk of dementia for survivors. Despite this massive global disease burden, there no approved drugs treating injury to brain oxygen deprivation occurring during an ischemic stroke. The precipitous drop pH resulting activates acid-sensing ion channel 1a. We show...
Acid-sensing ion channel 1a (ASIC1a) is a primary acid sensor in the peripheral and central nervous system. It has been implicated as novel therapeutic target for broad range of pathophysiological conditions including pain, ischemic stroke, depression, autoimmune diseases such multiple sclerosis. The only known selective blocker ASIC1a π-TRTX-Pc1a (PcTx1), disulfide-rich 40-residue peptide isolated from spider venom. an effective analgesic rodent models acute pain it provides neuroprotection...
Abstract ABC toxins are pore-forming virulence factors produced by pathogenic bacteria. YenTcA is the and membrane binding A subunit of toxin YenTc, insect pathogen Yersinia entomophaga . Here we present cryo-EM structures YenTcA, purified from native source. The soluble pre-pore structure, determined at an average resolution 4.4 Å, reveals a pentameric assembly that in contrast to other characterised formed two TcA-like proteins (YenA1 YenA2) decorated endochitinases (Chi1 Chi2). We also...
Background and Purpose The spider‐venom peptide PcTx1 is the most potent selective inhibitor of acid‐sensing ion channel (ASIC) 1a. It has centrally acting analgesic activity neuroprotective in rodent models ischaemic stroke. Understanding molecular details : ASIC1a interaction should facilitate development therapeutically useful modulators. Previously, we showed that several key pharmacophore residues reside a dynamic β‐hairpin loop; conclusions confirmed by recent crystal structures...
Acid-sensing ion channels (ASICs) are trimeric proton-gated cation that play a role in neurotransmission and pain sensation. The snake venom-derived peptides, mambalgins, exhibit potent analgesic effects rodents by inhibiting central ASIC1a peripheral ASIC1b. Despite their distinct species- subtype-dependent pharmacology, previous structure-function studies have focussed on the mambalgin interaction with ASIC1a. Currently, specific channel residues responsible for this pharmacological...
Bacterial ABC toxin complexes (Tcs) comprise three core proteins: TcA, TcB and TcC. The TcA protein forms a pentameric assembly that attaches to the surface of target cells penetrates cell membrane. TcC proteins assemble as heterodimeric TcB–TcC subcomplex makes hollow shell. This self-cleaves encapsulates within shell cytotoxic `cargo' encoded by C-terminal region protein. Here, we describe structure previously uncharacterized from Yersinia entomophaga , gene at distant genomic location...
<title>Abstract</title> Acid-sensing ion channels (ASICs) are trimeric proton-gated cation that play a role in neurotransmission and pain sensation. The snake venom-derived peptides, mambalgins, exhibit potent analgesic effects rodents by inhibiting central ASIC1a peripheral ASIC1b. Despite their distinct species- subtype-dependent pharmacology, previous structure-function studies have focussed on the mambalgin interaction with ASIC1a. Currently, specific channel residues responsible for...
Yersinia entomophaga is a naturally occurring, Gram negative insect pathogen, first isolated from the diseased larvae of New Zealand grass grub C. zealandica decade ago [1].Its main virulence determinant YenTc, heterogenous 2.4 MDa toxin complex that prototypical example ABC or Tc family predominantly insecticidal toxins.YenTc unique amongst members this family, in it only member class toxins characterised to date has broad target host range, and which exhibits potent oral activity towards...