Peri active site catalysis of proline isomerisation is the molecular basis of allomorphy in β-phosphoglucomutase.

Metabolic regulation occurs through precise control of enzyme activity. Allomorphy is a post-translational fine control mechanism where the catalytic rate is governed by a conformational switch that shifts the enzyme population between forms with different activities. β-Phosphoglucomutase (βPGM) uses allomorphy in the catalysis of isomerisation of β-glucose 1-phosphate to glucose 6-phosphate via β-glucose 1,6-bisphosphate.

Molecular basis of specificity and deamidation of eIF4A by Burkholderia Lethal Factor 1.

Burkholderia pseudomallei lethal factor 1 (BLF1) exhibits site-specific glutamine deamidase activity against the eukaryotic RNA helicase, eIF4A, thereby blocking mammalian protein synthesis. The structure of a complex between BLF1 C94S and human eIF4A shows that the toxin binds in the cleft between the two RecA-like eIF4A domains forming interactions with residues from both and with the scissile amide of the target glutamine, Gln339, adjacent to the toxin active site. The RecA-like domains adopt a radically twisted orientation compared to other eIF4A structures and the nature and position of conserved residues suggests this may represent a conformation associated with RNA binding.

Joint effects of climate, tree size, and year on annual tree growth derived from tree-ring records of ten globally distributed forests.

Tree rings provide an invaluable long-term record for understanding how climate and other drivers shape tree growth and forest productivity. However, conventional tree-ring analysis methods were not designed to simultaneously test effects of climate, tree size, and other drivers on individual growth. This has limited the potential to test ecologically relevant hypotheses on tree growth sensitivity to environmental drivers and their interactions with tree size.

PUP (Patient Is Up) Smart Sock Technology Prevents Falls Among Hospital Patients With High Fall Risk in a Clinical Trial and Observational Study.

Hospital inpatient falls, especially of older adult patients, can result in injury and death and generate high costs. A new technology, PUP (Patient Is Up) Smart Socks, combines sensors and geolocation in socks with a wireless platform. To determine whether these socks prevent falls of patients with high fall risk, we performed a clinical trial at one hospital, and an observational study at two other hospitals.

Compound climate extremes driving recent sub-continental tree mortality in northern Australia have no precedent in recent centuries.

Compound climate extremes (CCEs) can have significant and persistent environmental impacts on ecosystems. However, knowledge of the occurrence of CCEs beyond the past ~ 50 years, and hence their ecological impacts, is limited. Here, we place the widespread 2015-16 mangrove dieback and the more recent 2020 inland native forest dieback events in northern Australia into a longer historical context using locally relevant palaeoclimate records.

The effect of species, size, and fire intensity on tree mortality within a catastrophic bushfire complex.

Infrequent, high-intensity disturbances can have profound impacts on forested landscapes, changing forest structure and altering relative species abundance. However, due to their rarity and the logistical challenges of directly observing such extreme events, both the spatial variability of disturbance intensity and the species-specific responses to this variability are poorly understood. We used observed patterns of mortality across a fire severity gradient following the 2009 Black Saturday fires in southeastern Australia to simultaneously estimate (1) species- and size-specific susceptibility to fire-induced mortality and (2) fire intensity.

The structure of a major surface antigen SAG19 from Eimeria tenella unifies the Eimeria SAG family.

In infections by apicomplexan parasites including Plasmodium, Toxoplasma gondii, and Eimeria, host interactions are mediated by proteins including families of membrane-anchored cysteine-rich surface antigens (SAGs) and SAG-related sequences (SRS). Eimeria tenella causes caecal coccidiosis in chickens and has a SAG family with over 80 members making up 1% of the proteome. We have solved the structure of a representative E.

Characterisation of a tripartite α-pore forming toxin from Serratia marcescens.

Tripartite members of the ClyA family of α-PFTs have recently been identified in a number of pathogenic Gram-negative bacteria, including the human pathogen Serratia marcescens. Structures of a Gram-negative A component and a tripartite α-PFT complete pore are unknown and a mechanism for pore formation is still uncertain. Here we characterise the tripartite SmhABC toxin from S.

The A component (SmhA) of a tripartite pore-forming toxin from Serratia marcescens: expression, purification and crystallographic analysis.

Tripartite α-pore-forming toxins are constructed of three proteins (A, B and C) and are found in many bacterial pathogens. While structures of the B and C components from Gram-negative bacteria have been described, the structure of the A component of a Gram-negative α-pore-forming toxin has so far proved elusive. SmhA, the A component from the opportunistic human pathogen Serratia marcescens, has been cloned, overexpressed and purified.

The molecular basis of endolytic activity of a multidomain alginate lyase from , a representative of a new lyase family, PL39.

Alginate is a polymer containing two uronic acid epimers, β-d-mannuronate (M) and α-l-guluronate (G), and is a major component of brown seaweed that is depolymerized by alginate lyases. These enzymes have diverse specificity, cleaving the chain with endo- or exotype activity and with differential selectivity for the sequence of M or G at the cleavage site. Dp0100 is a 201-kDa multimodular, broad-specificity endotype alginate lyase from the marine thermophile , which uses brown algae as a carbon source, converting it to ethanol, and bioinformatics analysis suggested that its catalytic domain represents a new polysaccharide lyase family, PL39.

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The alpha helical CytolysinA family of pore forming toxins (α-PFT) contains single, two, and three component members. Structures of the single component Eschericia coli ClyA and the two component Yersinia enterolytica YaxAB show both undergo conformational changes from soluble to pore forms, and oligomerization to produce the active pore. Here we identify tripartite α-PFTs in pathogenic Gram negative bacteria, including Aeromonas hydrophila (AhlABC).

Distant Non-Obvious Mutations Influence the Activity of a Hyperthermophilic Phosphoglucose Isomerase.

The cupin-type phosphoglucose isomerase (PfPGI) from the hyperthermophilic archaeon catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate. We investigated PfPGI using protein-engineering bioinformatics tools to select functionally-important residues based on correlated mutation analyses. A pair of amino acids in the periphery of PfPGI was found to be the dominant co-evolving mutation.

Structural insights into the function of type VI secretion system TssA subunits.

The type VI secretion system (T6SS) is a multi-protein complex that injects bacterial effector proteins into target cells. It is composed of a cell membrane complex anchored to a contractile bacteriophage tail-like apparatus consisting of a sharpened tube that is ejected by the contraction of a sheath against a baseplate. We present structural and biochemical studies on TssA subunits from two different T6SSs that reveal radically different quaternary structures in comparison to the dodecameric E.

TssA from Aeromonas hydrophila: expression, purification and crystallographic studies.

TssA is a core subunit of the type VI secretion system, which is a major player in interspecies competition in Gram-negative bacteria. Previous studies on enteroaggregative Escherichia coli TssA suggested that it is comprised of three putative domains: a conserved N-terminal domain, a middle domain and a ring-forming C-terminal domain. X-ray studies of the latter two domains have identified their respective structures.

TssA from Burkholderia cenocepacia: expression, purification, crystallization and crystallographic analysis.

TssA is a core component of the type VI secretion system, and phylogenetic analysis of TssA subunits from different species has suggested that these proteins fall into three distinct clades. Whilst representatives of two clades, TssA1 and TssA2, have been the subjects of investigation, no members of the third clade (TssA3) have been studied. Constructs of TssA from Burkholderia cenocepacia, a representative of clade 3, were expressed, purified and subjected to crystallization trials.

Structural and functional studies of histidine biosynthesis in Acanthamoeba spp. demonstrates a novel molecular arrangement and target for antimicrobials.

Acanthamoeba is normally free-living, but sometimes facultative and occasionally opportunistic parasites. Current therapies are, by necessity, arduous and yet poorly effective due to their inabilities to kill cyst stages or in some cases to actually induce encystation. Acanthamoeba can therefore survive as cysts and cause disease recurrence.

Elucidating the structural basis for differing enzyme inhibitor potency by cryo-EM.

Histidine biosynthesis is an essential process in plants and microorganisms, making it an attractive target for the development of herbicides and antibacterial agents. Imidazoleglycerol-phosphate dehydratase (IGPD), a key enzyme within this pathway, has been biochemically characterized in both (IGPD) and (IGPD). The plant enzyme, having been the focus of in-depth structural analysis as part of an inhibitor development program, has revealed details about the reaction mechanism of IGPD, whereas the yeast enzyme has proven intractable to crystallography studies.

The molecular basis of phosphite and hypophosphite recognition by ABC-transporters.

Inorganic phosphate is the major bioavailable form of the essential nutrient phosphorus. However, the concentration of phosphate in most natural habitats is low enough to limit microbial growth. Under phosphate-depleted conditions some bacteria utilise phosphite and hypophosphite as alternative sources of phosphorus, but the molecular basis of reduced phosphorus acquisition from the environment is not fully understood.

Pnc1 piggy-back import into peroxisomes relies on Gpd1 homodimerisation.

Peroxisomes are eukaryotic organelles that posttranslationally import proteins via one of two conserved peroxisomal targeting signal (PTS1 or 2) mediated pathways. Oligomeric proteins can be imported via these pathways but evidence is accumulating that at least some PTS1-containing monomers enter peroxisomes before they assemble into oligomers. Some proteins lacking a PTS are imported by piggy-backing onto PTS-containing proteins.

Conserved residues in Ycf54 are required for protochlorophyllide formation in sp. PCC 6803.

Chlorophylls (Chls) are modified tetrapyrrole molecules, essential for photosynthesis. These pigments possess an isocyclic E ring formed by the Mg-protoporphyrin IX monomethylester cyclase (MgPME-cyclase). We assessed the effects of altering seven highly conserved residues within Ycf54, which is required for MgPME-cyclase activity in the cyanobacterium strains harbouring the Ycf54 alterations D39A, F40A and R82A were blocked to varying degrees at the MgPME-cyclase step, whereas the A9G mutation reduced Ycf54 levels by ∼75%.

The mechanism of a formaldehyde-sensing transcriptional regulator.

Most organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. Therefore, biology has evolved systems to perceive and detoxify formaldehyde. The frmRA(B) operon that is present in many bacteria represents one such system.

The paleoclimate context and future trajectory of extreme summer hydroclimate in eastern Australia.

Eastern Australia recently experienced an intense drought (Millennium Drought, 2003-2009) and record-breaking rainfall and flooding (austral summer 2010-2011). There is some limited evidence for a climate change contribution to these events, but such analyses are hampered by the paucity of information on long-term natural variability. Analyzing a new reconstruction of summer (December-January-February) Palmer Drought Severity Index (the Australia-New Zealand Drought Atlas; ANZDA, 1500-2012 CE), we find moisture deficits during the Millennium Drought fall within the range of the last 500 years of natural hydroclimate variability.

Mirror-Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of Enantiomers of an Experimental Herbicide.

Programs of drug discovery generally exploit one enantiomer of a chiral compound for lead development following the principle that enantiomer recognition is central to biological specificity. However, chiral promiscuity has been identified for a number of enzyme families, which have shown that mirror-image packing can enable opposite enantiomers to be accommodated in an enzyme's active site. Reported here is a series of crystallographic studies of complexes between an enzyme and a potent experimental herbicide whose chiral center forms an essential part of the inhibitor pharmacophore.

Establishing a Wild, Ex Situ Population of a Critically Endangered Shade-Tolerant Rainforest Conifer: A Translocation Experiment.

Translocation can reduce extinction risk by increasing population size and geographic range, and is increasingly being used in the management of rare and threatened plant species. A critical determinant of successful plant establishment is light environment. Wollemia nobilis (Wollemi pine) is a critically endangered conifer, with a wild population of 83 mature trees and a highly restricted distribution of less than 10 km2.