Spatial disposition

The spatial conformation that the ligand-receptor acquires, particularly the spatial disposition that helix 12 of the LBD attains when it binds to estradiol, is key for the subsequent recruitment of the transcription cofactors (Fig. 1.9). Indeed, the arrival of estradiol restructures the entire domain, making helix 12 rotate and close the hole where the leucine zipper sequence of the corepressor had been lodged before (Fig. 1.10). Consequently, both molecules, corepressor and receptor, lose their affinity and their bond is undone. Another structure capable of interacting with gene transcription coactivators is formed at the same place on the receptor (MacGregor et al. 1998 McDonnell et al. 2002). 

Three-dimensional (3-D) descriptors of molecules quantify their shape, size, and other structural characteristics which arise out of the 3-D disposition and orientation of atoms and functional groups of molecules in space. A special class of 3-D indices is quantitative descriptors of chirality. If a molecule has one or more chiral centers, the spatial disposition of atoms can produce enantiomers, many of which will have the same magnitude of calculated and experimental physicochemical properties having, at the same time, distinct bioactivity profiles. Basak and coworkers [22] have developed quantitative chirality indices to discriminate such isomers according to their structural invariants which are based on the Cahn-Ingold-Prelog (CIP) rules. 

Many protein molecules exist in two (or more) different structures of the same molecular mass but with different spatial disposition of constituent atoms. An intensively studied enzyme, aspartate transcarbamoylase (abbreviated ATCase), under some circumstances is in an enzymatically less-active constrained steric arrangement, which is labeled the T form, and under other conditions in the enzymatically very active, structurally more swollen and open conformation, the R form. 

For complexes 27 and 29, which contain the bpz dpz ligand, structural architectures that differ markedly from those of the previous complexes were found. The spatial disposition of the two pairs of chelating nitrogen atoms in the pyridazine derivative ligand causes the [Cu4L4 moieties to have, firstly, much shorter intramolecular Cu-Cu distances (ca. 3.6 A, see Table 3.1) and, secondly, also favors a nearly parallel alignment of opposite ligands L. As a result of these two features, the... 

Many monosaccharides possess at least two binding sites, by which they may be distinguished from each other. Thus, by careful manipulation of the spatial disposition of two 2-aminomethylphenylboronic acid groups, it should be possible to con-... 

Circular dichroism (CD) and optical rotatory dispersion (ORD) spectra (71PMH(3)397) are very sensitive to the spatial disposition of the atoms in a molecule, and conformational changes may yield rather dramatic changes in the appearance of a CD or ORD spectrum of a chiral molecule. The analysis of the temperature dependence of the CD spectrum may give information on populations and free energy differences. Except for nucleosides, the use of the chiroptical method in conformational analysis is rather limited, which may be accounted for by the complexity of the theory for optical activity. 

In solving problems of enzyme catalysis, molecular biophysics of proteins, biomembranes and molecular biology it is necessary to know the spatial disposition of individual parts. One must also know the depth of immersion of paramagnetic centers in a biological matrix, i.e. the availability of enzyme sites to substrates, distance of electron tunneling between a donor and an acceptor group, position of a spin-label in a membrane and in a protein globule, distribution of the electrostatic field around the PC, etc. 

One of the advantages of supramolecular chemistry over the covalent molecular approach resides in the possibility of inducing and/or transferring properties from singular molecules to self-organized multi-molecular assemblies. Chirality is one of these properties it stems from the electronic level (the helical nature of the electron rearrangement during a transition in chiral chromophores) and spreads up to the three-dimensional spatial disposition of atoms, or molecular components in molecular or supramolecular entities, respectively. 

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