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The role of the second shell in the process of metal binding and selectivity in metalloproteins has been elucidated by combining Protein Data Bank (PDB) surveys of Mg, Mn, Ca, and Zn binding sites with density functional theory/continuum dielectric methods (DFT/CDM). Peptide backbone groups were found to be the most common second-shell ligand in Mg, Mn, Ca,(More)
This review highlights insights gained from computational studies on protein-metal recognition. We systematically dissect the various factors governing metal binding affinity and selectivity in proteins starting from (a) the intrinsic properties of the metal and neighboring metal cations (if present), to (b) the primary coordination sphere, (c) the second(More)
Lithium is used (in the form of soluble salts) to treat bipolar disorder and has been considered as a possible drug in treating chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. One of the proposed mechanisms of Li(+) action involves a competition between the alien Li(+) and native Mg(2+) for metal-binding sites(More)
Ion channels, specialized pore-forming proteins, are an indispensable component of the nervous system and play a crucial role in regulating cardiac, skeletal, and smooth muscle contraction. Potassium ion channels, controlling the action potential of a number of excitable cells, are characterized by a remarkable ability to select K(+) over Na(+). Although(More)
Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the(More)
We delineate the factors governing the carboxylate-binding mode (monodentate vs bidentate) in metalloproteins. We reveal how the carboxylate-binding mode affects the binding affinity and selectivity of a metal ion as well as the function of a metalloprotein using Ca2+-binding proteins and enzymes (ribonuclease H1, phosphoserine phosphatase, and(More)
Structural and thermodynamic aspects of alkaline earth metal dication (Mg(2+), Ca(2+), Sr(2+), Ba(2+)) binding to E. coli ribonuclease H1 (RNase H1) have been investigated using both experimental and theoretical methods. The various metal-binding modes of the enzyme were explored using classical molecular dynamics simulations, and relative binding free(More)
The metal coordination number (CN) is a key determinant of the structure and properties of metal complexes. It also plays an important role in metal selectivity in certain metalloproteins. Despite its central role, the preferred CN for several metal cations remains ambiguous, and the factors determining the metal CN are not fully understood. Here, we(More)