Engineering Synthetic Electron Transfer Chains from Metallopeptide Membranes.

The energetic and geometric features enabling redox chemistry across the copper cupredoxin fold contain key components of electron transfer chains (ETC), which have been extended here by templating the cross-β bilayer assembly of a synthetic nonapeptide, HHQALVFFA-NH (K16A), with copper ions. Similar to ETC cupredoxin plastocyanin, these assemblies contain copper sites with blue-shifted ( 573 nm) electronic transitions and strongly oxidizing reduction potentials. Electron spin echo envelope modulation and X-ray absorption spectroscopies define square planar Cu(II) sites containing a single His ligand.

Mobilization of Iron Stored in Bacterioferritin Is Required for Metabolic Homeostasis in .

Iron homeostasis offers a significant bacterial vulnerability because pathogens obtain essential iron from their mammalian hosts, but host-defenses maintain vanishingly low levels of free iron. Although pathogens have evolved mechanisms to procure host-iron, these depend on well-regulated iron homeostasis. To disrupt iron homeostasis, our work has targeted iron mobilization from the iron storage protein bacterioferritin (BfrB) by blocking a required interaction with its cognate ferredoxin partner (Bfd).

β-Cyclodextrin Encapsulation of Synthetic AHLs: Drug Delivery Implications and Quorum-Quenching Exploits.

Many bacteria, such as Pseudomonas aeruginosa, regulate phenotypic switching in a population density-dependent manner through a phenomenon known as quorum sensing (QS). For Gram-negative bacteria, QS relies on the synthesis, transmission, and perception of low-molecular-weight signal molecules that are predominantly N-acyl-l-homoserine lactones (AHLs). Efforts to disrupt AHL-mediated QS have largely focused on the development of synthetic AHL analogues (SAHLAs) that are structurally similar to native AHLs.

The SDHB Arg230His mutation causing familial paraganglioma alters glycolysis in a new model.

The conserved B-subunit of succinate dehydrogenase (SDH) participates in the tricarboxylic acid cycle (TCA) cycle and mitochondrial electron transport. The Arg230His mutation in SDHB causes heritable pheochromocytoma/paraganglioma (PPGL). In , we generated an PPGL model (SDHB-1 Arg244His; equivalent to human Arg230His), which manifests delayed development, shortened lifespan, attenuated ATP production and reduced mitochondrial number.

COVID-19 meets Cystic Fibrosis: for better or worse?

Cystic fibrosis (CF) is one of the most common autosomal recessive life-limiting conditions affecting Caucasians. The resulting defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) results in defective chloride and bicarbonate secretion, as well as dysregulation of epithelial sodium channels (ENaC). These changes bring about defective mucociliary clearance, reduced airway surface liquid and an exaggerated proinflammatory response driven, in part, by infection.

Codon Harmonization of a Kir3.1-KirBac1.3 Chimera for Structural Study Optimization.

The expression of functional, folded, and isotopically enriched membrane proteins is an enduring bottleneck for nuclear magnetic resonance (NMR) studies. Indeed, historically, protein yield optimization has been insufficient to allow NMR analysis of many complex Eukaryotic membrane proteins. However, recent work has found that manipulation of plasmid codons improves the odds of successful NMR-friendly protein production.

Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis.

Previously, we showed that serum and monocytes from patients with CF exhibit an enhanced NLRP3-inflammasome signature with increased IL-18, IL-1β, caspase-1 activity and ASC speck release (Scambler et al. eLife 2019). Here we show that CFTR modulators down regulate this exaggerated proinflammatory response following LPS/ATP stimulation.

Molecular complementarity and structural heterogeneity within co-assembled peptide β-sheet nanofibers.

Self-assembling peptides have garnered an increasing amount of interest as a functional biomaterial for medical and biotechnological applications. Recently, β-sheet peptide designs utilizing complementary pairs of peptides composed of charged amino acids positioned to impart co-assembly behavior have expanded the portfolio of peptide aggregate structures. Structural characterization of these charge-complementary peptide co-assemblies has been limited.

Guest Inclusion Modulates Concentration and Persistence of Photogenerated Radicals in Assembled Triphenylamine Macrocycles.

Substituted triphenylamine (TPA) radical cations show great potential as oxidants and as spin-containing units in polymer magnets. Their properties can be further tuned by supramolecular assembly. Here, we examine how the properties of photogenerated radical cations, intrinsic to TPA macrocycles, are altered upon their self-assembly into one-dimensional columns.

Electrostatic Complementarity Drives Amyloid/Nucleic Acid Co-Assembly.

Proteinaceous plaques associated with neurodegenerative diseases contain many biopolymers including the polyanions glycosaminoglycans and nucleic acids. Polyanion-induced amyloid fibrillation has been implicated in disease etiology, but structural models for amyloid/nucleic acid co-assemblies remain limited. Here we constrain nucleic acid/peptide interactions with model peptides that exploit electrostatic complementarity and define a novel amyloid/nucleic acid co-assembly.

Investigating the genetic diversity and presence of forensically informative nucleotide sequences in Indian antelope (Antilope cervicapra) using multiple genes of the mitochondrial genome.

Indian antelope or Blackbuck (Antilope cervicapra) is one of the widely distributed endemic species in India among wild bovids and a majority of preferred habitats are in human-dominated landscapes. Poaching threats and habitat degradation are major factors for the decline in Blackbuck population from its distribution range. Till date, there is no detailed study using molecular techniques in India on Blackbuck, except a few studies entailing phylogenetic scenario based on inadequate sampling and DNA sequences restricted over limited geographic areas.

The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/Dynamin.

Phagocytosis of various targets, such as apoptotic cells or opsonized pathogens, by macrophages is coordinated by a complex signaling network initiated by distinct phagocytic receptors. Despite the different initial signaling pathways, each pathway ends up regulating the actin cytoskeletal network, phagosome formation and closure, and phagosome maturation leading to degradation of the engulfed particle. Herein, we describe a new phagocytic function for the nucleoside diphosphate kinase 1 (NDK-1), the nematode counterpart of the first identified metastasis inhibitor NM23-H1 (nonmetastatic clone number 23) nonmetastatic clone number 23 or nonmetastatic isoform 1 (NME1).

NMR Crystallography: Evaluation of Hydrogen Positions in Hydromagnesite by C{ H} REDOR Solid-State NMR and Density Functional Theory Calculation of Chemical Shielding Tensors.

Solid-state NMR measurements coupled with density functional theory (DFT) calculations demonstrate how hydrogen positions can be refined in a crystalline system. The precision afforded by rotational-echo double-resonance (REDOR) NMR to interrogate C- H distances is exploited along with DFT determinations of the C tensor of carbonates (CO ). Nearby H nuclei perturb the axial symmetry of the carbonate sites in the hydrated carbonate mineral, hydromagnesite [4 MgCO ⋅Mg(OH) ⋅4 H O].

Species dilemma of musk deer ( spp) in India: molecular data on cytochrome oxidase I suggests distinct genetic lineage in Uttarakhand compared to other species.

Musk deer are of high conservation priority owing to poaching pressure because of its musk pod. Representation of musk deer status using genetics is poorly documented in India, and it is not confirmed as to how many species of musk deer are present. We characterize for the first time, the genetic diversity of musk deer from Uttarakhand using Cytochrome Oxidase sub-unit (COI) gene (486 bp) and compared with the data available for other species.

Emerging contaminants in a river receiving untreated wastewater from an Indian urban centre.

Research over the last decade on emerging trace organic contaminants in aquatic systems has largely focused on sources such as treated wastewaters in high income countries, with relatively few studies relating to wastewater sources of these contaminants in low and middle income countries. We undertook a longitudinal survey of the Ahar River for a number of emerging organic contaminants (including pharmaceuticals, hormones, personal care products and industrial chemicals) which flows through the city of Udaipur, India. Udaipur is a city of approximately 450,000 people with no wastewater treatment occurring at the time of this survey.

Creating longitudinal datasets and cleaning existing data identifiers in a cystic fibrosis registry using a novel Bayesian probabilistic approach from astronomy.

Patient registry data are commonly collected as annual snapshots that need to be amalgamated to understand the longitudinal progress of each patient. However, patient identifiers can either change or may not be available for legal reasons when longitudinal data are collated from patients living in different countries. Here, we apply astronomical statistical matching techniques to link individual patient records that can be used where identifiers are absent or to validate uncertain identifiers.

DNA barcoding as a tool for robust identification of cervids of India and its utility in wildlife forensics.

DNA barcoding has become a popular method of choice for identification of specimen based on molecular techniques. Here, we present preliminary findings on generating robust DNA barcode library of Cervids of India. The dataset comprising the DNA barcode library of seven deer species included in the genus and classified under family Cervidae.

NM23 proteins: innocent bystanders or local energy boosters for CFTR?

NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function.

Expanding the informational chemistries of life: peptide/RNA networks.

The RNA world hypothesis simplifies the complex biopolymer networks underlining the informational and metabolic needs of living systems to a single biopolymer scaffold. This simplification requires abiotic reaction cascades for the construction of RNA, and this chemistry remains the subject of active research. Here, we explore a complementary approach involving the design of dynamic peptide networks capable of amplifying encoded chemical information and setting the stage for mutualistic associations with RNA.

Multistep Conformation Selection in Amyloid Assembly.

Defining pathways for amyloid assembly could impact therapeutic strategies for as many as 50 disease states. Here we show that amyloid assembly is subject to different forces regulating nucleation and propagation steps and provide evidence that the more global β-sheet/β-sheet facial complementarity is a critical determinant for amyloid nucleation and structural selection.

Polyoxometalate-based gelating networks for entrapment and catalytic decontamination.

We report the synthesis and characterization of a new class of organic/inorganic hybrid polymers composed of covalently-bound 1,3,5-benzenetricarboxamide linkers and anionic polyoxovanadate clusters with varying counter-cations. These materials form gels within seconds upon contact with polar aprotic organic liquids and catalyze the degradation of odorants and toxic molecules under mild conditions including aerobic oxidation of thiols, hydrogen peroxide-catalyzed oxidation of sulfides, and hydrolysis of organophosphate chemical warfare agent analogues.

Purifying Properly Folded Cysteine-rich, Zinc Finger Containing Recombinant Proteins for Structural Drug Targeting Studies: the CH1 Domain of p300 as a Case Example.

The transcription factor Hypoxia-Inducible Factor (HIF) complexes with the coactivator p300, activating the hypoxia response pathway and allowing tumors to grow. The CH1 and CAD domains of each respective protein form the interface between p300 and HIF. Small molecule compounds are in development that target and inhibit HIF/p300 complex formation, with the goal of reducing tumor growth.

The dosage-dependent effect exerted by the NM23-H1/H2 homolog NDK-1 on distal tip cell migration in C. elegans.

Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is involved in these processes. NM23-H1 inhibits the migratory and invasive potential of some cancer cells.