An atlas of Arabidopsis protein S-acylation reveals its widespread role in plant cell organization and function.

S-acylation is the addition of a fatty acid to a cysteine residue of a protein. While this modification may profoundly alter protein behaviour, its effects on the function of plant proteins remains poorly characterized, largely as a result of the lack of basic information regarding which proteins are S-acylated and where in the proteins the modification occurs. To address this gap in our knowledge, we used an optimized acyl-resin-assisted capture assay to perform a comprehensive analysis of plant protein S-acylation from six separate tissues.

Levoglucosenone and Its Pseudoenantiomer -Levoglucosenone as Scaffolds for Drug Discovery and Development.

The bioderived platform molecule levoglucosenone (LGO, ) and its readily prepared pseudoenantiomer (-LGO, ) have each been subjected to α-iodination reactions with the product halides then being engaged in palladium-catalyzed Ullmann cross-coupling reactions with various bromonitropyridines. The corresponding α-pyridinylated derivatives such as and , respectively, are produced as a result. Biological screening of such products reveals that certain of them display potent and selective antimicrobial and/or cytotoxic properties.

Author Correction: Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

GPI Anchored Proteins in Aspergillus fumigatus and Cell Wall Morphogenesis.

Glycosylphosphatidylinositol (GPI) anchored proteins are a class of proteins attached to the extracellular leaflet of the plasma membrane via a post-translational modification, the glycolipid anchor. GPI anchored proteins are expressed in all eukaryotes, from fungi to plants and animals. They display very diverse functions ranging from enzymatic activity, signaling, cell adhesion, cell wall metabolism, and immune response.

The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus.

The frequency of antifungal resistance, particularly to the azole class of ergosterol biosynthetic inhibitors, is a growing global health problem. Survival rates for those infected with resistant isolates are exceptionally low. Beyond modification of the drug target, our understanding of the molecular basis of azole resistance in the fungal pathogen Aspergillus fumigatus is limited.

Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme.

Characterizing the adaptive landscapes that encompass the emergence of novel enzyme functions can provide molecular insights into both enzymatic and evolutionary mechanisms. Here, we combine ancestral protein reconstruction with biochemical, structural and mutational analyses to characterize the functional evolution of methyl-parathion hydrolase (MPH), an organophosphate-degrading enzyme. We identify five mutations that are necessary and sufficient for the evolution of MPH from an ancestral dihydrocoumarin hydrolase.

Cryptic genetic variation shapes the adaptive evolutionary potential of enzymes.

Genetic variation among orthologous proteins can cause cryptic phenotypic properties that only manifest in changing environments. Such variation may impact the evolvability of proteins, but the underlying molecular basis remains unclear. Here, we performed comparative directed evolution of four orthologous metallo-β-lactamases toward a new function and found that different starting genotypes evolved to distinct evolutionary outcomes.

FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress.

The ability to persist in the absence of growth triggered by low oxygen levels is a critical process for the survival of mycobacterial species in many environmental niches. (), a gene of unknown function in , is up-regulated in response to hypoxia and regulated by DosRDosS/DosT, an oxygen- and redox-sensing two-component system that is highly conserved in mycobacteria. In this communication, we demonstrate that MSMEG_5243 is a lavin-uestering protein and henceforth refer to it as Fsq.

Syntheses of Structurally and Stereochemically Varied Forms of CN Aminocyclitol Derivatives from Enzymatically Derived and Homochiral cis-1,2-Dihydrocatechols.

The structurally and stereoisomerically varied CN aminocyclitol derivatives 2-4 have been prepared, using a versatile and flexible range of protocols, from the cis-1,2-dihydrocatechols 5 and 6, homochiral metabolites derived from the whole-cell biotransformation of the corresponding halobenzene. Reaction sequences that enable syntheses of the enantiomeric forms of these derivatives have also been established.

The evolution of multiple active site configurations in a designed enzyme.

Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase.

Synthesis, X-ray Structural Characterization, and DFT Calculations of Mononuclear Nickel(II) Complexes Containing Diamine and Methacrylate Ligands.

The mononuclear Ni(II) complexes [Ni(en)2(H2O)2](MAA)2 (1) and [Ni(pn)2(MAA)2] (2), where MAA, en and pn are methacrylate, ethylendiamine and 1,3-propylendiamine, respectively, have been synthesized and characterized by elemental analysis, FT-IR and UV�Vis spectroskopy. Structures of the complexes have been determined by single-crystal X-ray diffraction analyses. In the nickel(II) complexes 1 and 2 nickel(II) ion is six-coordinate and has a distorted octahedral geometry.

Evolution of cyclohexadienyl dehydratase from an ancestral solute-binding protein.

The emergence of enzymes through the neofunctionalization of noncatalytic proteins is ultimately responsible for the extraordinary range of biological catalysts observed in nature. Although the evolution of some enzymes from binding proteins can be inferred by homology, we have a limited understanding of the nature of the biochemical and biophysical adaptations along these evolutionary trajectories and the sequence in which they occurred. Here we reconstructed and characterized evolutionary intermediate states linking an ancestral solute-binding protein to the extant enzyme cyclohexadienyl dehydratase.

Palladium-Catalyzed Ullmann Cross-Coupling of β-Iodoenones and β-Iodoacrylates with o-Halonitroarenes or o-Iodobenzonitriles and Reductive Cyclization of the Resulting Products To Give Diverse Heterocyclic Systems.

The palladium-catalyzed Ullmann cross-coupling of β-iodoenones and β-iodoacrylates such as 5 (X = I) with o-halonitroarenes and o-iodobenzonitriles including 2 affords products such as compound 7. These can be engaged in a range of reductive cyclization reactions leading to heterocyclic frameworks such as 3,4-benzomorphan derivative 43.

Mechanistic Basis of pH-Dependent 5-Flucytosine Resistance in Aspergillus fumigatus.

The antifungal drug 5-flucytosine (5FC), a derivative of the nucleobase cytosine, is licensed for the treatment of fungal diseases; however, it is rarely used as a monotherapeutic to treat infection. Despite being potent against other fungal pathogens, 5FC has limited activity against when standard assays are used to determine susceptibility. However, in modified assays where the pH is set to pH 5, the activity of 5FC increases significantly.

Exploiting CELLULOSE SYNTHASE (CESA) Class Specificity to Probe Cellulose Microfibril Biosynthesis.

Cellulose microfibrils are the basic units of cellulose in plants. The structure of these microfibrils is at least partly determined by the structure of the cellulose synthase complex. In higher plants, this complex is composed of 18 to 24 catalytic subunits known as CELLULOSE SYNTHASE A (CESA) proteins.

Structure of an Insecticide Sequestering Carboxylesterase from the Disease Vector Culex quinquefasciatus: What Makes an Enzyme a Good Insecticide Sponge?

Carboxylesterase (CBE)-mediated metabolic resistance to organophosphate and carbamate insecticides is a major problem for the control of insect disease vectors, such as the mosquito. The most common mechanism involves overexpression of CBEs that bind to the insecticide with high affinity, thereby sequestering them before they can interact with their target. However, the absence of any structure for an insecticide-sequestering CBE limits our understanding of the molecular basis for this process.

Synthesis, X-ray Structural Characterization, and DFT Calculations of Binuclear Mixed-ligand Copper(II) Complexes Containing Diamine, Acetate and Methacrylate Ligands.

The dinuclear Cu(II) complexes [Cu(en)(MAA)(μ-CH3COO)]2 (1) and [Cu(pn)(MAA)(μ-CH3COO)]2 (2) where MAA, en and pn are methacrylate, ethylendiamine and 1,3-propylendiamine, respectively, have been synthesized and characterized by elemental analysis, FT-IR and UV-Vis spectroscopy. The structures of the complexes have been determined by single-crystal X-ray diffraction analyses. In the dinuclear complexes 1 and 2 the two copper centers are five-coordinated and exhibit distorted square pyramidal geometries.

Total Synthesis of the Cyclic Carbonate-Containing Natural Product Aspergillusol B from d-(-)-Tartaric Acid.

A total synthesis of compound 3 from d-(-)-tartaric acid is reported, thereby establishing that the structure, including relative stereochemistry, originally assigned to the cyclic carbonate-containing natural product aspergillusol B is correct.

Studies on the Photochemical Rearrangements of Enantiomerically Pure, Polysubstituted, and Variously Annulated Bicyclo[2.2.2]octenones.

A series of enantiomerically pure bicyclo[2.2.2]octenones, including the lactone-annulated system 26, has been prepared by engaging derivatives of an enzymatically derived and homochiral cis-1,2-dihydrocatechol in inter- or intra-molecular Diels-Alder reactions.

The Synthesis of Certain Derivatives and Analogues of (-)- and (+)-Galanthamine and an Assessment of their Capacities to Inhibit Acetylcholine Esterase.

Syntheses of certain di- and mono-oxygenated derivatives (e.g., 2 and 3, respectively) and analogues (e.

A Total Synthesis of (±)-3-O-Demethylmacronine through Rearrangement of a Precursor Embodying the Haemanthidine Alkaloid Framework.

A total synthesis of the racemic modification, (±)-2, of the tazettine-type alkaloid 3-O-demethylmacronine is described. The key steps are an intramolecular Alder-ene (IMAE) reaction and a lactam-to-lactone rearrangement of tetracycle 13, a compound that embodies the haemanthidine alkaloid framework.

A Unified Approach to the Isomeric α-, β-, γ-, and δ-Carbolines via their 6,7,8,9-Tetrahydro Counterparts.

A cross-coupling/reductive cyclization protocol has been employed in a unified approach to all four carbolines. So, for example, the 2-nitropyridine 8, which is readily prepared through an efficient palladium-catalyzed Ullmann cross-coupling reaction, is reductively cyclized under conventional conditions to give 6,7,8,9-tetrahydro-α-carboline that is itself readily aromatized to give α-carboline (1).

A Palladium-Catalyzed Ullmann Cross-Coupling/Reductive Cyclization Route to the Carbazole Natural Products 3-Methyl-9H-carbazole, Glycoborine, Glycozoline, Clauszoline K, Mukonine, and Karapinchamine A.

The title natural products 2-7 have been prepared by reductive cyclization of the relevant 2-arylcyclohex-2-en-1-one (e.g. 20) to the corresponding tetrahydrocarbazole and dehydrogenation (aromatization) of this to give the target carbazole (e.

Correction: Sterol Biosynthesis and Azole Tolerance Is Governed by the Opposing Actions of SrbA and the CCAAT Binding Complex.

[This corrects the article DOI: 10.1371/journal.ppat.