A5025793442- Enzyme Structure and Function
- Trace Elements in Health
- Biochemical and Molecular Research
- Metalloenzymes and iron-sulfur proteins
- Photosynthetic Processes and Mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Porphyrin Metabolism and Disorders
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- Peptidase Inhibition and Analysis
- Legume Nitrogen Fixing Symbiosis
- Iron Metabolism and Disorders
- Amino Acid Enzymes and Metabolism
- Chemical Reactions and Isotopes
- Plant Micronutrient Interactions and Effects
- Metal complexes synthesis and properties
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Drug Transport and Resistance Mechanisms
- Metabolism and Genetic Disorders
- Chromium effects and bioremediation
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
La Trobe University
2013-2023
The University of Melbourne
1999-2023
Bowdoin College
2016
Imperial College London
2007-2012
Centenary Institute
2008-2012
The University of Sydney
2000-2011
Walter and Eliza Hall Institute of Medical Research
2009
Boston Children's Hospital
2008
University of Georgia
2004
University of Saskatchewan
2003
Abstract Cadmium is a transition metal ion that highly toxic in biological systems. Although relatively rare the Earth’s crust, anthropogenic release of cadmium since industrialization has increased biogeochemical cycling and abundance biosphere. Despite this, molecular basis its toxicity remains unclear. Here we combine metal-accumulation assays, high-resolution structural data biochemical analyses to show toxicity, Streptococcus pneumoniae , occurs via perturbation first row homeostasis....
Biogenesis of complex IV the mitochondrial respiratory chain requires assembly factors for subunit maturation, co-factor attachment and stabilization intermediate assemblies. A pathogenic mutation in COA6, leading to substitution a conserved tryptophan cysteine residue, results loss activity cardiomyopathy. Here, we demonstrate that defect correlates with severe patient heart but not fibroblasts. Complete COA6 using gene editing HEK293T cells resulted profound growth due deficiency, caused...
CopC is a small soluble protein expressed in the periplasm of Pseudomonas syringae pathovar tomato as part its copper resistance response (cop operon). Equilibrium competition reactions confirmed two separated binding sites with high affinities for CuI (10-7 ≥ KD 10-13 M) and CuII (KD = 10-13(1) M), respectively. While CuI-CopC was converted cleanly by O2 to CuII-CopC, fully loaded form CuICuII-CopC stable air. Variant forms H1F H91F exhibited lower affinity than does wild-type while variant...
Bioenergy is efficiently produced in the mitochondria by respiratory system consisting of complexes I–V. In various organisms, complex I can be replaced alternative NADH-quinone oxidoreductase (NDH-2), which catalyzes transfer an electron from NADH via FAD to quinone, without proton pumping. The Ndi1 protein Saccharomyces cerevisiae a monotopic membrane protein, directed matrix. A number studies have investigated potential use as therapeutic agent against disorders, and NDH-2 enzymes emerged...
Abstract WalKR (YycFG) is the only essential two-component regulator in human pathogen Staphylococcus aureus . regulates peptidoglycan synthesis, but this function alone does not explain its essentiality. Here, to further understand function, we investigate a suppressor mutant that arose when activity was impaired; histidine tyrosine substitution (H271Y) cytoplasmic Per-Arnt-Sim (PAS CYT ) domain of kinase WalK. Introducing WalK H271Y mutation into wild-type S. activates regulon. Structural...
Streptococcus pneumoniae is the primary cause of community-acquired bacterial pneumonia with rates penicillin and multidrug-resistance exceeding 80% 40%, respectively. The innate immune response generates a variety antimicrobial agents to control infection, including zinc stress. Here, we characterize impact intoxication on S. pneumoniae, observing disruptions in central carbon metabolism, lipid biogenesis, peptidoglycan biosynthesis. Characterization pivotal biosynthetic enzyme GlmU...
Cytochrome c oxidase (COX) assembly factor 7 (COA7) is a metazoan-specific factor, critical for the biogenesis of mitochondrial complex IV (cytochrome oxidase). Although mutations in COA7 have been linked to defects and neurological conditions such as peripheral neuropathy, ataxia, leukoencephalopathy, precise role plays not known. Here, we show that loss blocks after initial step where COX1 module built, progression from which requires incorporation copper addition COX2 COX3 modules. The...
Lepidopterans affect crop production worldwide. The use of transgenes encoding insecticidal proteins from Bacillus thuringiensis ( Bt ) in plants is a well-established technology that enhances protection against lepidopteran larvae. Concern about widespread field-evolved resistance to has highlighted an urgent need for new with different modes or sites action. We discovered family ferns. prototype protein Pteris species (Order Polypodiales) and variants two other orders ferns, Schizaeales...
The structure of prolidase from the hyperthermophilic archaeon Pyrococcus furiosus (Pfprol) has been solved and refined at 2.0 A resolution. This is first a prolidase, i.e., peptidase specific for dipeptides having proline as second residue. asymmetric unit crystals contains homodimer enzyme. Each two protein subunits domains. C-terminal domain includes catalytic site, which centered on dinuclear metal cluster. In as-isolated form Pfprol, active-site atoms are Co(II) [Ghosh, M., et al....
FeoB is a prokaryotic membrane protein responsible for the import of ferrous iron (Fe2+). A defining feature that it includes an N-terminal 30-kDa soluble domain with GTPase activity, which required transport. However, low intrinsic GTP hydrolysis rate this appears to be too slow either function as channel or possess active Fe2+ transport mechanism. Here, we present crystal structures from Streptococcus thermophilus in complex GDP and analogue derivative 2′-(or...
Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import pathway many micronutrients including first-row transition metal manganese. However, structural features ionic transporting ABC have remained undefined. Here, we present crystal structure manganese transporter PsaBC from
The acid-induced arginine decarboxylase is part of an enzymatic system in Escherichia coli that contributes to making this organism acid resistant. a vitamin B(6)-dependent enzyme active at acidic pH. It consumes proton the decarboxylation agmatine, and by working tandem with arginine-agmatine antiporter, cycle protects preventing accumulation protons inside cell. We have determined structure X-ray crystallography 2.4 A resolution. revealed ca. 800 kDa decamer composed as pentamer five...
G‐proteins are some of the most important and abundant enzymes, yet their intrinsic nucleotide hydrolysis reaction is notoriously slow must be accelerated in vivo. Recent experiments on dynamin GTPases involved ribosome assembly have demonstrated that activities stimulated by potassium ions. This article presents hypothesis cation‐mediated activation more common than currently realised, such represent a structurally functionally unique class G‐proteins. Based sequence analysis we provide...
The bacterium Cupriavidus metallidurans CH34 is resistant to high environmental concentrations of many metal ions, including copper. This ability arises primarily from the presence a large plasmid pMOL30 which includes cluster 19 cop genes that respond One protein products CopK induced at levels and expressed periplasm as small soluble (8.3 kDa). Apo-CopK associates in solution form dimer (K(D) approximately 10(-5) M) whose structure was defined by NMR X-ray crystallography. individual...
The polytopic membrane protein FeoB is a ferrous iron transporter in prokaryotes. contains potassium-activated GTPase domain that essential regulating the import of and conferring virulence to many disease-causing bacteria. However, mechanism by which G-domain hydrolyzes GTP not well understood. In particular, it yet known how pivotal step hydrolysis achieved: alignment catalytic water molecule. current study, crystal structure soluble domains from Streptococcus thermophilus (NFeoBSt)...
Interprotein electron transfer underpins the essential processes of life and relies on formation specific, yet transient protein-protein interactions. In biological systems, detoxification sulfite is catalyzed by sulfite-oxidizing enzymes (SOEs), which interact with an acceptor for catalytic turnover. Here, we report structural functional analyses SOE SorT from Sinorhizobium meliloti its cognate SorU. Kinetic thermodynamic SorT/SorU interaction show complex dynamic in solution, that proteins...
The CopC protein from Pseudomonas syringae pathovar tomato is expressed as one of four proteins encoded by the operon CopABCD that responsible for copper resistance. It a small soluble molecule (10.5 kDa) with β-barrel structure and features two distinct binding sites, which are highly specific CuI (KD ≥ 10-13) CuII ≈ 10-15). These dissociation constants were estimated via ligand competition experiments monitored electronic spectral fluorescence probes. chemistries sites interdependent. When...