Three-dimensional structures Volume

Good A C and J S Mason 1995. Three-Dimensional Structure Database Searches. In Lipkowitz K B and D B Boyd (Editors) Reviews in Computational Chemistry Volume 7. New York, VCH Publishers, pp. 67-117. 

The two isozymes are both homodimers, composed of approximately 600 amino acids and possess approximately 60% homology. The three-dimensional structures of COX-1 and COX-2 are very similar. Each one consists of three independent units an epidermal growth factor-like domain, a membrane-binding section and an enzymic domain. The catalytic sites and the residues immediately adjacent are identical but for two small but crucial variations that result in an increase in the volume of the COX-2-active site, enabling it to accept inhibitor-molecules larger than those that could be accommodated in the COX-1 molecule. 

This procedure was repeated for HRV-1A. Duplicate maps were generated by means of both procedures and clearly show that shorter molecules, as measured from the phenoxy to isoxazole moieties, are more active. Molecules with the correct degree and placement of bulk in the middle of the volume are also more active. These encouraging results suggest that this method can be applied to other serotypes without giving consideration to their three-dimensional structures. 

A fundamental goal of research in the biological sciences is to understand protein structure. In theory, protein sequence information can be inferred from the fast growing volume of DNA sequence data [1] but predicting the three-dimensional structure of a protein from its sequence remains an open and important problem [2 1]. Part of the difficulty in solving this problem is due to the fact that many of the existing techniques rely on our knowledge of previously determined structures which, compared to sequence data, is relatively limited. 

Molecular structure determines the gross activity of an organic compound, as it is responsible for the molecular volume, water solubility, vapor pressure, density, and electrical charge of the compound. The three-dimensional structure of an organic... 

As outlined in other chapters in this volume, Tomalia et al. first reported the successful well-characterized synthesis of dendrimers in the early 1980s [1], These molecules range in size from 10 A to 130 A in diameter for generation 0 (GO) through generation 10 (G10). In the ideal situation, PAMAM dendrimers are monodispersed spherical conformation with a highly branched three-dimensional structure (Figure 18.1) that provides a scaffold for the attachment of... 

Molecular modeling techniques are a powerful tool to obtain a very detailed insight in the three-dimensional structure of dendrimer molecules at the atomic level. They have been applied to calculate sizes of the polypropylene imine) dendrimers and radial density profiles in order to estimate the free volume inside the dendrimers, as well as to make predictions about de Gennes dense-packed generations. The molecular modeling work by Coussens and co-workers [20] was focused on the generations 1-5 of the DAB-dendr-(CN)n and DAB-dendr-(NH2)n (n = 4, 8, 16,32, 64). 

The regeneration of specific tissues aided by synthetic materials has been shown to be dependent on the porosity and pore size of the supporting three-dimensional structure. A large surface area favors cell attachment and growth, whereas a large pore volume is required to accommodate and subsequently deliver a cell mass sufficient... 

In addition to interest in this enzyme because of its catalytic characteristics, a considerable body of information has accumulated on staphylococcal nuclease as a protein molecule. Its relatively small size, the absence of covalent cross-linkages, and its behavior upon binding a variety of ligands have made it an ideal model substance for the study of various aspects of protein chemistry including X-ray crystallography. These investigations are reviewed in the present chapter and in Chapter 7 by Cotton and Hazen, this volume, on the three-dimensional structure (19). 

Work is well under way on the high resolution structure of the uninhibited nuclease as are attempts to prepare crystals with other mono-, di-, and trinucleotides of various types so that more insight may be gained into the actual workings of the nuclease. As described elsewhere in this volume (25), some of the most exciting prospects for the future are the correlations to he made between the crystallographic studies of the three-dimensional structure and the properties of the fragmented and synthetic versions of this nuclease. 

Branched polymers have side chains, or branches, of significant length which are bonded to the main chain at branch points (also known as jimction points), and are characterised in terms of the number and size of the branches. Network polymers have three-dimensional structures in which each chain is connected to all others by a sequence of junction points and other chains. Such polymers are said to be crosslinked and are characterised by their crosslink density, or degree of crosslinking, which is related directly to the number of junction points per unit volume. 

---