A Bis(imidazole)-based cysteine labeling tool for metalloprotein assembly.

Precise metal-protein coordination by design remains a considerable challenge. Polydentate, high-metal-affinity protein modifications, both chemical and recombinant, can enable metal localization. However, these constructs are often bulky, conformationally and stereochemically ill-defined, or coordinately saturated.

Design of a minimal di-nickel hydrogenase peptide.

Ancestral metabolic processes involve the reversible oxidation of molecular hydrogen by hydrogenase. Extant hydrogenase enzymes are complex, comprising hundreds of amino acids and multiple cofactors. We designed a 13-amino acid nickel-binding peptide capable of robustly producing molecular hydrogen from protons under a wide variety of conditions.

A redox-active Mn(0) dicarbene metalloradical.

We report a rare redox-active Mn metalloradical [Mn(CO)(PhB(NHC))] (NHC = N-heterocyclic carbene) with countercations [K(2.2.2)crypt], [Na(2.

Biophysical Characterization of Iron-Sulfur Proteins.

Iron-sulfur proteins are primordial catalysts and biological electron carriers that today drive major metabolic pathways across all forms of life. They can access a diversity of oxidation states and can mediate electron transfer over an extended range of reduction potentials spanning more than 1 V. Depending on the protein micro-environment and geometry of ligand, co-ordination the iron-sulfur clusters can occur in different forms [2Fe-2S], [3Fe-4S], HiPIP [4Fe-4S], and [4Fe-4S].

Accessing three oxidation states of cobalt in ML nanoprisms with cobalt-porphyrin walls.

Nanocages with porphyrin walls are common, but studies of such structures hosting redox-active metals are rare. Pt-linked ML nanoprisms with cobalt-porphyrin walls were prepared and their redox properties were evaluated electrochemically and chemically, leading to the first time that cobalt-porphyrin nanocages have been characterized in Co, Co, and Co states.

Inhibition of GATA2 in prostate cancer by a clinically available small molecule.

Castration-resistant prostate cancer (CRPC) remains highly lethal and in need of novel, actionable therapeutic targets. The pioneer factor GATA2 is a significant prostate cancer (PC) driver and is linked to poor prognosis. GATA2 directly promotes androgen receptor (AR) gene expression (both full-length and splice-variant) and facilitates AR binding to chromatin, recruitment of coregulators, and target gene transcription.

Biogenesis of a Designed Iron-Sulfur Protein.

expression of metalloproteins requires specific metal trafficking and incorporation machinery inside the cell. Synthetic designed metalloproteins are typically purified without the target metal, which is subsequently introduced through reconstitution. The extra step complicates protein optimization by high-throughput library screening or laboratory evolution.

Design of a Fe S cluster into the core of a de novo four-helix bundle.

We explore the capacity of the de novo protein, S824, to incorporate a multinuclear iron-sulfur cluster within the core of a single-chain four-helix bundle. This topology has a high intrinsic designability because sequences are constrained largely by the pattern of hydrophobic and hydrophilic amino acids, thereby allowing for the extensive substitution of individual side chains. Libraries of novel proteins based on these constraints have surprising functional potential and have been shown to complement the deletion of essential genes in E.

Post-Transcriptional Regulation of Alpha One Antitrypsin by a Proteasome Inhibitor.

Alpha one antitrypsin (α1AT), a serine proteinase inhibitor primarily produced by the liver, protects pulmonary tissue from neutrophil elastase digestion. Mutations of the gene results in a misfolded α1AT protein which aggregates inside hepatocytes causing cellular damage. Therefore, inhibition of mutant α1AT production is one practical strategy to alleviate liver damage.

A Blinking Mesoporous TiO Composed of Nanosized Anatase with Unusually Long-Lived Trapped Charge Carriers.

A mesoporous TiO material comprised of small, crystalline, vacancy-rich anatase nanoparticles (NPs) shows unique optical, thermal, and electronic properties. It is synthesized using polymer-derived mesoporous carbon (PDMC) as a template. The PDMC pores serve as physical barriers during the condensation and pyrolysis of a titania precursor, preventing the titania NPs from growing beyond 10 nm in size.

De novo design of symmetric ferredoxins that shuttle electrons in vivo.

A symmetric origin for bacterial ferredoxins was first proposed over 50 y ago, yet, to date, no functional symmetric molecule has been constructed. It is hypothesized that extant proteins have drifted from their symmetric roots via gene duplication followed by mutations. Phylogenetic analyses of extant ferredoxins support the independent evolution of N- and C-terminal sequences, thereby allowing consensus-based design of symmetric 4Fe-4S molecules.

Minimal Heterochiral de Novo Designed 4Fe-4S Binding Peptide Capable of Robust Electron Transfer.

Ambidoxin is a designed, minimal dodecapeptide consisting of alternating L and D amino acids that binds a 4Fe-4S cluster through ligand-metal interactions and an extensive network of second-shell hydrogen bonds. The peptide can withstand hundreds of oxidation-reduction cycles at room temperature. Ambidoxin suggests how simple, prebiotic peptides may have achieved robust redox catalysis on the early Earth.

Observation of an environmentally insensitive solid-state spin defect in diamond.

Engineering coherent systems is a central goal of quantum science. Color centers in diamond are a promising approach, with the potential to combine the coherence of atoms with the scalability of a solid-state platform. We report a color center that shows insensitivity to environmental decoherence caused by phonons and electric field noise: the neutral charge state of silicon vacancy (SiV).

All-electric control of donor nuclear spin qubits in silicon.

The electronic and nuclear spin degrees of freedom of donor impurities in silicon form ultra-coherent two-level systems that are potentially useful for applications in quantum information and are intrinsically compatible with industrial semiconductor processing. However, because of their smaller gyromagnetic ratios, nuclear spins are more difficult to manipulate than electron spins and are often considered too slow for quantum information processing. Moreover, although alternating current magnetic fields are the most natural choice to drive spin transitions and implement quantum gates, they are difficult to confine spatially to the level of a single donor, thus requiring alternative approaches.

Electron Spin Coherence of Shallow Donors in Natural and Isotopically Enriched Germanium.

Germanium is a widely used material for electronic and optoelectronic devices and recently it has become an important material for spintronics and quantum computing applications. Donor spins in silicon have been shown to support very long coherence times (T_{2}) when the host material is isotopically enriched to remove any magnetic nuclei. Germanium also has nonmagnetic isotopes so it is expected to support long T_{2}'s while offering some new properties.

Anisotropic stark effect and electric-field noise suppression for phosphorus donor qubits in silicon.

We report the use of novel, capacitively terminated coplanar waveguide resonators to measure the quadratic Stark shift of phosphorus donor qubits in Si. We confirm that valley repopulation leads to an anisotropic spin-orbit Stark shift depending on electric and magnetic field orientations relative to the Si crystal. By measuring the linear Stark effect, we estimate the effective electric field due to strain in our samples.

SRC kinase is a novel therapeutic target in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease affecting some women with tuberous sclerosis complex (TSC). Sporadic LAM can develop in women without TSC, owing to somatic mutations in the TSC2 gene. Accumulating evidence supports the view of LAM as a low-grade, destructive, metastasizing neoplasm.

Atomic clock transitions in silicon-based spin qubits.

A major challenge in using spins in the solid state for quantum technologies is protecting them from sources of decoherence. This is particularly important in nanodevices where the proximity of material interfaces, and their associated defects, can play a limiting role. Spin decoherence can be addressed to varying degrees by improving material purity or isotopic composition, for example, or active error correction methods such as dynamic decoupling (or even combinations of the two).

Superconducting coplanar waveguide resonators for low temperature pulsed electron spin resonance spectroscopy.

We discuss the design and implementation of thin film superconducting coplanar waveguide micro-resonators for pulsed electron spin resonance experiments. The performance of the resonators with P doped Si epilayer samples is compared to waveguide resonators under equivalent conditions. The high achievable filling factor even for small sized samples and the relatively high Q-factor result in a sensitivity of 4.

Electron spin coherence exceeding seconds in high-purity silicon.

Silicon is one of the most promising semiconductor materials for spin-based information processing devices. Its advanced fabrication technology facilitates the transition from individual devices to large-scale processors, and the availability of a (28)Si form with no magnetic nuclei overcomes a primary source of spin decoherence in many other materials. Nevertheless, the coherence lifetimes of electron spins in the solid state have typically remained several orders of magnitude lower than that achieved in isolated high-vacuum systems such as trapped ions.

Electrically detected magnetic resonance of neutral donors interacting with a two-dimensional electron gas.

We have measured the electrically detected magnetic resonance of donor-doped silicon field-effect transistors in resonant X- (9.7 GHz) and W-band (94 GHz) microwave cavities. The two-dimensional electron gas resonance signal increases by 2 orders of magnitude from X to W band, while the donor resonance signals are enhanced by over 1 order of magnitude.

Coherent state transfer between an electron and nuclear spin in (15)N@C(60).

Electron spin qubits in molecular systems offer high reproducibility and the ability to self-assemble into larger architectures. However, interactions between neighboring qubits are "always on," and although the electron spin coherence times can be several hundred microseconds, these are still much shorter than typical times for nuclear spins. Here we implement an electron-nuclear hybrid scheme which uses coherent transfer between electron and nuclear spin degrees of freedom in order to both effectively turn on or off interqubit coupling mediated by dipolar interactions and benefit from the long nuclear spin decoherence times (T(2n)).

Regulation of NF-kappaB activity and inducible nitric oxide synthase by regulatory particle non-ATPase subunit 13 (Rpn13).

Human Rpn13, also known as adhesion regulating molecule 1 (ADRM1), was recently identified as a novel 19S proteasome cap-associated protein, which recruits the deubiquitinating enzyme UCH37 to the 26S proteasome. Knockdown of Rpn13 by siRNA does not lead to global accumulation of ubiquitinated cellular proteins or changes in proteasome expression, suggesting that Rpn13 must have a specialized role in proteasome function. Thus, Rpn13 participation in protein degradation, by recruiting UCH37, is rather selective to specific proteins whose degradation critically depends on UCH37 deubiquitination activity.

Src kinase-mediated phosphorylation stabilizes inducible nitric-oxide synthase in normal cells and cancer cells.

Src kinases are key regulators of cellular proliferation, survival, motility, and invasiveness. They play important roles in the regulation of inflammation and cancer. Overexpression or hyperactivity of c-Src has been implicated in the development of various types of cancer, including lung cancer.

Kinetic model for Ca2+-induced permeability transition in energized liver mitochondria discriminates between inhibitor mechanisms.

Cytotoxicity associated with pathophysiological Ca(2+) overload (e.g. in stroke) appears mediated by an event termed the mitochondrial permeability transition (mPT).