Protein Ca-Sites Prone to Sr Substitution: Implications for Strontium Therapy.

Strontium (Sr), an alkali metal with properties similar to calcium, in the form of soluble salts is used to treat osteoporosis. Despite the information accumulated on the role of Sr as a Ca mimetic in biology and medicine, there is no systematic study of how the outcome of the competition between the two dications depends on the physicochemical properties of (i) the metal ions, (ii) the first- and second-shell ligands, and (iii) the protein matrix. Specifically, the key features of a Ca-binding protein that enable Sr to displace Ca remain unclear.

From quantum-derived principles underlying cysteine reactivity to combating the COVID-19 pandemic.

The COVID-19 pandemic poses a challenge in coming up with quick and effective means to counter its cause, the SARS-CoV-2. Here, we show how the key factors governing cysteine reactivity in proteins derived from combined quantum mechanical/continuum calculations led to a novel multi-targeting strategy against SARS-CoV-2, in contrast to developing potent drugs/vaccines against a single viral target such as the spike protein. Specifically, they led to the discovery of reactive cysteines in evolutionary conserved Zn-sites in several SARS-CoV-2 proteins that are crucial for viral polypeptide proteolysis as well as viral RNA synthesis, proofreading, and modification.

Trophectoderm biopsy protocols can affect clinical outcomes: time to focus on the blastocyst biopsy technique.

Objective: To compare two different blastocyst biopsy protocols.

Design: Retrospective single-center cohort study.

Settings: Private in vitro fertilization center.

How First Shell-Second Shell Interactions and Metal Substitution Modulate Protein Function.

Hydrogen bonds to metal-ligands in proteins play a vital role in biological function. They help to stabilize/protect the metal complex and enhance metal-binding affinity/specificity, enzyme-substrate recognition, and enzyme activation. Yet, knowledge of the preferred hydrogen-bonding partners of metal ligands in different metalloproteins is lacking.

Competition between Li and Na in sodium transporters and receptors: Which Na-Binding sites are "therapeutic" Li targets?

Sodium (Na) acts as an indispensable allosteric regulator of the activities of biologically important neurotransmitter transporters and G-protein coupled receptors (GPCRs), which comprise well-known drug targets for psychiatric disorders and addictive behavior. How selective these allosteric Na-binding sites are for the cognate cation over abiogenic Li, a first-line drug to treat bipolar disorder, is unclear. Here, we reveal how properties of the host protein and its binding cavity affect the outcome of the competition between Li and Na for allosteric binding sites in sodium transporters and receptors.

Factors controlling the selectivity for Na(+) over Mg(2+) in sodium transporters and enzymes.

Na(+) and Mg(2+) play different crucial roles in biological systems. Both cations are present in comparable amounts in the cytosol, but how monovalent Na(+) can compete with the divalent Mg(2+), which can better accept charge from negatively charged ligands, in sodium transporters/enzymes has not been investigated. Hence, it is not clear how Na(+) and Mg(2+)-binding sites have evolved to discriminate the "right" cation among non-cognate ones from the surrounding milieu and the physical basis governing the selectivity for Na(+) over Mg(2+).

Selectivity Mechanism of the Voltage-gated Proton Channel, HV1.

Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown.

Diagnostics of psychophysiological states and motivation in elite athletes.

Objectives: Concepts explored in our study concerned identification of various types of motivation and their connection to psychophysiological states in elite judo and Greco-Roman wrestlers. We tried to figure out how do these different types of motivation interact to describe psychophysiological state in qualified wrestlers.

Methods: Neuropsychological evaluation methods as simple (SRT) and choice reaction-time (CRT) tests, HRV measurements, psychological questionnaires.