Spectroscopic and functional characterization of the [2Fe-2S] scaffold protein Nfu from Synechocystis PCC6803.

Iron-sulfur clusters are ubiquitous cofactors required for various essential metabolic processes. Conservation of proteins required for their biosynthesis and trafficking allows for simple bacteria to be used as models to aid in exploring these complex pathways in higher organisms. Cyanobacteria are among the most investigated organisms for these processes, as they are unicellular and can survive under photoautotrophic and heterotrophic conditions.

Active site characterization and activity of the human aspartyl (asparaginyl) β-hydroxylase.

Human aspartyl/asparaginyl beta-hydroxylase (HAAH) is a member of the superfamily of nonheme Fe2+/α-ketoglutarate (αKG) dependent oxygenase enzymes with a noncanonical active site. HAAH hydroxylates epidermal growth factor (EGF) like domains to form the β-hydroxylated product from substrate asparagine or aspartic acid and has been suggested to have a negative impact in a variety of cancers. In addition to iron, HAAH also binds divalent calcium, although the role of the latter is not understood.

Enhanced Synergism and Mechanism of Action Studies of Synthetic Antimicrobial Metallopeptides.

Antimicrobial peptides (AMPs) are found throughout most kingdoms of life, are an important part of host immunity, and have been shown to act synergistically in various organisms to ameliorate bacterial infections. Herein, we report the synergistic behavior observed between two AMPs, Sub5 and CP10A, against E. coli.

Biochemical impact of a disease-causing Ile67Asn substitution on BOLA3 protein.

Iron-sulfur (Fe-S) cluster biosynthesis involves the action of a variety of functionally distinct proteins, most of which are evolutionarily conserved. Mutations in these Fe-S scaffold and trafficking proteins can cause diseases such as multiple mitochondrial dysfunctions syndrome (MMDS), sideroblastic anemia, and mitochondrial encephalopathy. Herein, we investigate the effect of Ile67Asn substitution in the BOLA3 protein that results in the MMDS2 phenotype.

Metalloglycosidase Mimics: Oxidative Cleavage of Saccharides Promoted by Multinuclear Copper Complexes under Physiological Conditions.

Degradation of saccharides is relevant to the design of catalytic therapeutics, the production of biofuels, inhibition of biofilms, as well as other applications in chemical biology. Herein, we report the design of multinuclear Cu complexes that enable cleavage of saccharides under physiological conditions. Reactivity studies with -nitrophenyl (NP)-conjugated carbohydrates show that dinuclear Cu complexes exhibit a synergistic effect and promote faster and more robust cleavage of saccharide substrates, relative to the mononuclear Cu complex, while no further enhancement is observed for the tetranuclear Cu complex.

Artificial Metalloenzymes: Recent Developments and Innovations in Bioinorganic Catalysis.

Cellular life is orchestrated by the biochemical components of cells that include nucleic acids, lipids, carbohydrates, proteins, and cofactors such as metabolites and metals, all of which coalesce and function synchronously within the cell. Metalloenzymes allow for such complex chemical processes, as they catalyze a myriad of biochemical reactions both efficiently and selectively, where the metal cofactor provides additional functionality to promote reactivity not readily achieved in their absence. While the past 60 years have yielded considerable insight on how enzymes catalyze these reactions, a need to engineer and develop artificial metalloenzymes has been driven not only by industrial and therapeutic needs, but also by innate human curiosity.

Cu-ATCUN Derivatives of Sub5 Exhibit Enhanced Antimicrobial Activity via Multiple Modes of Action.

Antimicrobial peptides (AMPs) are short, amphipathic peptides that are typically cationic in sequence and display broad-spectrum activity against bacteria, fungi, and protists. Herein, we report the effect of appending the amino terminal copper and nickel binding motif (ATCUN) to Sub5. The Cu-ATCUN derivatives show a two- to three-fold increase in antimicrobial activity for a variety of microbes, relative to Sub5, with MICs as low as 0.

Antimicrobial Metallopeptides.

Antimicrobial peptides are short amphipathic peptides that are produced by the innate immune system in order to protect a host from pathogens. They have been shown to have broad-spectrum antimicrobial activity toward Gram-positive and Gram-negative bacteria, as well as antifungal, antiprotozoan, and antiviral activity. These peptides are able to exert their activity through a variety of mechanisms that include inhibiting DNA and RNA replication, inhibiting protein synthesis, permeabilizing the cell membrane, disrupting proton and ion transmembrane gradients, and inhibiting cell wall biosynthesis.

Dust Library of Plasmonically Enhanced Infrared Spectra of Individual Respirable Particles.

This work characterizes collections of infrared spectra of individual dust particles of ∼4 µm size that were obtained from three very different environments: our lab air, a home air filter, and the 11 September 2001 World Trade Center event. Particle collection was done either directly from the air or by placing dust powder from various samples directly on the plasmonic mesh with 5 µm square holes as air is pumped through the mesh. This arrangement enables the recording of "scatter-free" infrared absorption spectra of individual particles of size comparable to the probing wavelengths whose vibrational signatures are otherwise dominated by scattering and dispersive line shape distortions.