Ligand binding small molecules

Cytochromes of the b and c groups usually have two strong field axial ligands and are therefore low-spin. These will not bind small molecules. Cytochromes a3 and d, in contrast, bind 02 and act as terminal oxidases. 

Riboswitches are RNA regulatory elements capable of binding small molecule metabolites to regulate the mRNA in which they are embedded (Montange and Batey, 2008 Winkler and Breaker, 2005). Our lab recently solved the crystal structure of the lysine riboswitch ligand-binding domain... 

Finally, the selected compounds are purchased or synthesized and then tested. If the goal is to identify weakly binding small molecules, it is important to ensure that the biological assay is sensitive and robust enough to pick up these molecules. Measurements using 100-1000 pM concentration of the ligand frequently cause problems due to the limited solubility of the ligands in water. To compensate for this, the assay is often carried out in the presence of 1-5% dimethyl sulfoxide (DMSO) (see, e.g.. Ref. 14). 

Considering the synthesis of an artificial system with coordinative or covalent bonds in square planar metal chelates for binding small molecules or catalytic use, main points are donor ligand activation, reduced aggregation, and irreversible oxidation of the chelate. 

Many proteins bind small molecules but do not catalyze a reaction of the ligand. Some examples include the binding of oxygen by myoglobin or hemoglobin and the binding of hormones and drugs by specific receptor... 

Of the large variety of protein pockets capable of binding small molecules with appreciable affinity, only a small fraction has been cocrystallized with at least one ligand. The majority of pockets of... 

It is appropriate at this point to indicate our personal motivation for carrying out structural studies, the types of compounds we study, and the experimental conditions we employ. In a very general sense we are interested in the bonding of small molecules and ions, e.g., 02, N2, NO, N2 R+, olefins, and acetylenes, to transition-metal complexes. Because of our interest in bonding, we seek the best solutions we can attain. Rapid, qualitative answers to conformational problems are not our interest. Since those transition-metal systems that bind small molecules generally have the metal in a low oxidation state, and since a low oxidation state is usually stabilized by ligands of the type PR3 (R = alkyl or aryl), solution to our problems involves typically the determination of a large number of structural parameters. With only a few exceptions the intensity data are obtained at room temperature on a Picker FACS-1 computer-controlled diffractometer. Usually the ratio of observations to variables is at least 10, and it is often 20 to 30. 

Several properties of transition metals make them useful in catalysis. Metal ions provide a high concentration of positive charge that is especially useful in binding small molecules. Because transition metals act as Lewis acids (electron pair acceptors), they are effective electrophiles. (Amino acid side chains are poor electrophiles because they cannot accept unshared pairs of electrons.) Because their directed valences allow them to interact with two or more ligands, metal ions help orient the substrate within the active site. As a consequence, the substrate-metal ion complex polarizes the substrate and promotes catalysis. For... 

Navratilova, I., Dioszegi, M., Myszka, D. G. (2006). Analyzing ligand and small molecule binding activity of solubilized GPCRs using biosensor technology. Analytical Biochemistry, 355, 132-139. 

---