Orientation of bound ligands

Ligand- macromolecule complex Stoichiometry of complex Kinetics of binding Location of interacting sites Orientation of bound ligand Structure of complex Dynamics of complex Chemical shift titration Line width, titration analysis HSQC, isotope editing NOE docking 3D/4D NMR Relaxation time measurements... 

The structure of the ligand-receptor complex defines the orientation of the ligand vwth respect to the cell membrane. The total surface area buried in the TNF-P-( TNFR)3 complex (1.120 A2) is about the same size as that in the hGH—(hGHbp)2 complex. Although the quaternary structures of fi ee and liganded TNF-P receptor are different, the structure and conformation of firee and bound ligand, TNF-P, are, like free and bound hGH, virtually identical, as shown by Naismith et cdP... 

Confinement. The ligand molecule is confined to a small volume and a narrow range of orientations, that correspond to the freedom of the ligand in the bound state. 

In refined structures at high resolution (around 2 A) there are usually no major errors in the orientation of individual residues, and the estimated errors in atomic positions are around 0.1-0.2 A provided the amino acid sequence is known. Hydrogen bonds both within the protein and to bound ligands can be identified with a high degree of confidence. 

Although anosmias to these compounds occur at similar levels, some communicative value may arise from the persistence of signal emissions which are not enantiomerically pure (Carman, 1993 Wysocki et al., 1999). In secreted mixtures, the alternate versions of such compounds are produced in a constant ratio since they have identical volatility and hence provide stable informational content to the receiver. Support for this idea comes from the results of the NMR mapping of the BT binding site within the MUP1 carrier (Zidek et al., 1999). Here the protein-ligand complex does exist in the expected ratio, and for both enantiomers, although the orientation of the bound thiazole was interpreted as opposite to that indicated by previous X-ray analyses. 

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