A5048370461- Enzyme Structure and Function
- Biochemical and Structural Characterization
- Enzyme Production and Characterization
- Enzyme Catalysis and Immobilization
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Microbial bioremediation and biosurfactants
- Pharmacogenetics and Drug Metabolism
- Eicosanoids and Hypertension Pharmacology
- DNA and Nucleic Acid Chemistry
- Advanced Chemical Physics Studies
- Histone Deacetylase Inhibitors Research
- Microbial Metabolic Engineering and Bioproduction
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Biotin and Related Studies
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Scientific Computing and Data Management
- Biochemical Acid Research Studies
- Signaling Pathways in Disease
The University of Western Australia
2005-2024
The University of Sydney
2016-2020
Murdoch University
2020
ARC Centre of Excellence in Plant Energy Biology
2018
University of Manchester
2016
Czech Academy of Sciences, Institute of Biotechnology
2016
Karolinska Institutet
2010-2015
Monash University
2007-2011
University of St Andrews
2010
ARC Centre of Excellence in Advanced Molecular Imaging
2010
Summary Plant asparaginyl endopeptidases ( AEP s) are expressed as inactive zymogens that perform maturation of seed storage protein upon cleavage‐dependent autoactivation in the low‐ pH environment vacuoles. The s have attracted attention for their macrocyclization reactions, and been classified cleavage or ligation specialists. However, we recently shown ability to produce either cyclic acyclic products can be altered by mutations active site region, several capable given favorable...
Abstract Members of the pentatricopeptide repeat (PPR) protein family act as specificity factors in C-to-U RNA editing. The expansion PPR superfamily plants provides sequence variation required for design consensus-based RNA-binding proteins. We used this approach to a synthetic editing factor target one sites Arabidopsis chloroplast transcriptome recognised by natural CHLOROPLAST BIOGENESIS 19 (CLB19). show that our specifically recognises vitro binding assays. designed is equally specific...
The nucleosome remodelling and deacetylase (NuRD) complex is essential for the development of animals. NuRD has roles in regulating gene expression repairing damaged DNA. comprises at least six proteins with two or more paralogues each protein routinely identified when purified from cell extracts. To understand structure function NuRD, a map direct subunit interactions needed. Dozens published studies have attempted to define inter-subunit connectivities. We propose that conclusions reported...
Constrained, cyclic peptides encoded by plant genes represent a new generation of drug leads. Evolution has repeatedly recruited the Cys-protease asparaginyl endopeptidase (AEP) to perform their head-to-tail ligation. These macrocyclization reactions use substrates amino terminus instead water deacylate, so peptide bond is formed. How solvent-exposed AEPs macrocyclize poorly understood. Here we present crystal structure an active AEP from common sunflower, Helianthus annuus. The site...
The nucleosome remodeling and deacetylase (NuRD) complex is essential for metazoan development but has been refractory to biochemical analysis. We present an integrated analysis of the native mammalian NuRD complex, combining quantitative mass spectrometry, cross-linking, protein biochemistry, electron microscopy define architecture complex. built from a 2:2:4 (MTA, HDAC, RBBP) module 1:1:1 (MBD, GATAD2, Chromodomain-Helicase-DNA-binding [CHD]) module, displays considerable structural...
Aberrant KRAS signaling is a driver of many cancers and yet remains an elusive target for drug therapy. The nuclease hypersensitive element the promoter has been reported to form secondary DNA structures called G-quadruplexes (G4s) which may play important roles in regulating expression, spurred interest structural elucidation studies G-quadruplexes. Here, we report first high-resolution crystal structure (1.6 Å) G-quadruplex as 5'-head-to-head dimer with extensive poly-A π-stacking...
Background A central tenet of structural biology is that related proteins common function share similarity. This has key practical consequences for the derivation and analysis protein structures, exploited by process "molecular sieving" whereby a core progressively distilled from comparison two or more structures. paper reports novel web server "sieving" based on multiple alignment program MUSTANG. Methodology/Principal Findings "Sieved" models are generated MUSTANG-generated superpositions...
It's a gas! The structure of the halomethane-producing halo/thiocyanate methyltransferase enzyme from plants has been determined. halide ion and methyl group S-adenosyl-L-methionine (SAM) were modeled into active site (see picture; chloride: green sphere; SAM: C green, O red, S yellow, N blue), which indicated their predisposition for reaction.
Bacterial infections are increasingly difficult to treat owing the spread of antibiotic resistance. A major concern is Gram-negative bacteria, for which discovery new antimicrobial drugs has been particularly scarce. In an effort accelerate early steps in drug discovery, EU-funded AEROPATH project aims identify novel targets opportunistic pathogen Pseudomonas aeruginosa by applying a multidisciplinary approach encompassing target validation, structural characterization, assay development and...
The nucleosome remodeling and deacetylase (NuRD) complex remodels the genome in context of both gene transcription DNA damage repair. It is essential for normal development distributed across multiple tissues organisms ranging from mammals to nematode worms. In common with other chromatin-remodeling complexes, however, its molecular mechanism action not well understood only limited structural information available show how assembled. As a step towards understanding structure NuRD complex, we...
Abstract Background Human g rowth factor r eceptor b ound protein 7 (Grb7) is an adapter that mediates the coupling of tyrosine kinases with their downstream signaling pathways. Grb7 frequently overexpressed in invasive and metastatic human cancers implicated cancer progression via its interaction ErbB2 receptor focal adhesion kinase (FAK) play critical roles cell proliferation migration. It thus a prime target for development novel anti-cancer therapies. Recently, inhibitory peptide...
There is a pressing need for the archiving and curation of raw X-ray diffraction data. This information critical validation, methods development improvement archived structures. However, relatively large size these data sets has presented challenges storage in single worldwide repository such as Protein Data Bank archive. problem can be avoided by using federated approach, where each institution utilizes its institutional storage, with discovery service overlaid. Institutional repositories...
Pentatricopeptide repeat (PPR) proteins are RNA-binding that attractive tools for RNA processing in synthetic biology applications given their modular structure and ease of design. Several distinct types motifs have been described from natural PPR proteins, but almost all work so far with has focused on the most widespread P-type motifs. We investigated based tandem repeats more compact S-type motif found plant organellar editing factors particularly prevalent lycophyte Selaginella. With aid...
Over 30 years ago, an intriguing posttranslational modification was found responsible for creating concanavalin A (conA), a carbohydrate-binding protein from jack bean (Canavalia ensiformis) seeds and common carbohydrate chromatography reagent. ConA biosynthesis involves what then unprecedented rearrangement in amino-acid sequence, whereby the N-terminal half of gene-encoded conA precursor (pro-conA) is swapped to become C-terminal conA. Asparaginyl endopeptidase (AEP) shown be involved, but...
Locus PA4043 in the genome of Pseudomonas aeruginosa PAO1 has been annotated as coding for a farnesyl pyrophosphate synthase (FPPS). This open reading frame was cloned and expressed recombinantly Escherichia coli . The dimeric enzyme shows activity is strongly inhibited by ibandronate zoledronate, drugs that are presently clinical use. structures unliganded complexes with substrate geranyl diphosphate (GPP), inhibitor two compounds obtained from differential scanning fluorimetry-based screen...
The combination of stable isotope labelling with direct infusion ion mobility mass spectrometry (IM-MS) enabled qualitative and quantitative monitoring biocatalytic reactions reduced analysis times, enhanced sensitivity μL-level assay volumes. new approach was demonstrated by applying to both lipase monooxygenase enzymes, including multi-substrate screening.
The phase transformations and structural changes occurring during initial heating annealing of an Ag-clad high-Tc superconducting tape the (Bi, Pb)2Sr2Ca2Cu3Ox type are investigated. takes place in air at operating temperature 835 °C. Using x-ray diffraction with 100 keV photons from a synchrotron source concentration, stoichiometry texture dominant phases monitored situ transformation BiSCCO Pb)2Sr2CaCu2Ox (2212) to (2223). In addition, information on grain size residual strain is obtained....
Aus der Pflanze in die Luft: Die Struktur des Halogenmethan erzeugenden pflanzlichen Enzyms Halogenid/Thiocyanat-Methyltransferase wurde bestimmt. Modellieren eines Halogenidions und Methylgruppe von S-Adenosyl-L-methionin (SAM) im aktiven Zentrum (siehe Bild; Chlorid: grüne Kugel; SAM: C grün, O rot, S gelb, N blau) zeigt deren Ausrichtung für Reaktion. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not...
Pentatricopeptide repeat proteins (PPR) are a large family of modular RNA-binding proteins, whereby each module can be modified to bind specific ssRNA nucleobase. As such, there is interest in developing 'designer' PPRs (dPPRs) for range biotechnology applications, including diagnostics or vivo localization species; however, the mechanistic details regarding how search and target sequences unclear. To address this, we determined structure dPPR bound its sequence used two- three-color...