Ligand binding hydrogen bonding

DeChancie, J., Houk, K. N. The origins of femtomolar protein-ligand binding hydrogen-bond cooperativity and desolvation energetics in the biotin-(strept)avidin binding site. J. Am. Chem. Soc. 2007, 129, 5419-5429. 

In this chapter, we will show how the concept of template-directed organic synthesis has expanded so that now metal-ligand binding, hydrogen bonding, n-n interactions, and covalent bonding can all be exploited to allow the synthesis of molecules with a remarkable degree of control. Several detailed reviews of molecular templates have been published [14-20]. This chapter explores the definition and classification of molecular templates and discusses how their performance can be quantified and optimized. 

The cluster is coordinated at the tip of the cluster binding subdomain. Fe" (Fe-2) is close to the surface of the protein with its histidine ligands fully exposed to the solvent, whereas Fe " (Fe-1) is buried within the protein and surrounded by the three loops forming the cluster binding subdomain. However, in NDO the histidine ligands are not solvent accessible, but buried at the interface between the Rieske domain and the catalytic domain both histidine ligands form hydrogen bonds with acidic side chains in the catalytic site close to the catalytic iron. 

The structure of the more active enantiomer (BMS270394) shows that the ligand binds to RAR-y in a typical agonist conformation (Fig. 1.24). The carboxylate group of the ligand forms hydrogen bonds to Ser-289 and a water molecule in the... 

Figure 12.5 Stereo view of 3,5-dichloro-3 -isopropyl-thyronine bound to the thyroid hormone receptor a. Details of the binding pocket dashed lines indicate stabilizing ligand-protein hydrogen bonds. See color plates.

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