Stability constants protein complexes

The next selection criterion concerns the polarity of the selected cavity. In the most favorable case, it should contain hydrophobic residues to favor the design of lipophilic inhibitors. The addition of hydrophobic substitutions (taking care to ensure their solubility) is an effective way of improving the potency of an inhibitor thanks to the hydrophobic effect. It has been shown that electrostatic interactions are important for the rate of association, but not for the stability of protein complexes [20], Furthermore, electrostatic interactions are weakened by the high dielectric constant of water. It might therefore be more difficult to identify inhibitors that bind tightly to the target cavity when it is essentially polar. 

Strohmeier W (1968) Problem und Modell der homogenen Katalyse. 5 96-117 Sugiura Y, Nomoto K (1984) Phytosiderophores - Structures and Properties of Mugineic Acids and Their Metal Complexes. 58 107-135 Sun H, Cox MC, Li H, Sadler PJ (1997) Rationalisation of Binding to Transferrin Prediction of Metal-Protein Stability Constants. 88 71-102 Swann JC, see Bray RC (1972) II 107-144... 

PROTEIN DISULFIDE ISOMERASE STABILITY CONSTANT METAL ION COMPLEXATION... 

Although there is some experimental evidence which points to a binding of iron ions by specific cytosolic proteins (see Cytosolic Iron Donor, below), these proteins, with the exception of transferrin, are available only in minute quantities, and the nature and extent of iron-protein interactions are poorly understood. Therefore, a number of nonprotein iron chelates have been studied as possible model donor complexes (Table I). Because of the high stability constants of, for example, the Fe(II)/Fe(III)-8-hydroxyquinoline and Fe(III)-ADP complexes (20), these iron-chelate complexes are unfavorable as iron donors, and in fact no energy-dependent uptake of iron has been detected using these complexes (21, 23). 

Here, the charge density of the metal ion plays a pivotal role in the stability constants. The first series contains metal ions of similar size but different charges, while the ions in the second series increase with size from Mg2+ to Ba2+. In both cases, ions with higher charge densities form stronger complexes. Sometimes ions with similar sizes and charge densities can be transported by the same transport proteins. For example, Cd2+ (0.97 A) can be transported via Ca2+ (0.99 A) channels. 

Some metals may need to be mobilized from the environment to make them bioavailable. Iron in particular must be rendered more soluble to be accessible for uptake. Microorganisms and some plants have evolved with secreted ligands known as siderophores (or phytosiderophores). These ligands bind Fe + with extraordinary affinity. For example, a complex of the siderophore enterobactin with ferric iron has a formal stability constant of 10 (19). Once siderophores compete with other environmental ligands for iron, the ferric iron-siderophore complex then binds to specific transport proteins at the microbial... 

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