Basic Principles of Protein Structure

Ithough knowledge-based potentials are most popular, it is also possible to use other types potential function. Some of these are more firmly rooted in the fundamental physics of iteratomic interactions whereas others do not necessarily have any physical interpretation all but are able to discriminate the correct fold from decoy structures. These decoy ructures are generated so as to satisfy the basic principles of protein structure such as a ose-packed, hydrophobic core [Park and Levitt 1996]. The fold library is also clearly nportant in threading. For practical purposes the library should obviously not be too irge, but it should be as representative of the different protein folds as possible. To erive a fold database one would typically first use a relatively fast sequence comparison lethod in conjunction with cluster analysis to identify families of homologues, which are ssumed to have the same fold. A sequence identity threshold of about 30% is commonly... 

The first six chapters of this book deal with the basic principles of protein structure as we understand them today, and examples of the different major classes of protein structures are presented. Chapter 7 contains a brief discussion on DNA structures with emphasis on recognition by proteins of specific nucleotide sequences. The remaining chapters illustrate how during evolution different structural solutions have been selected to fulfill particular functions. 

The structure and function of enzymes is determined by both the amino acid sequence and the surrounding solvent. The overall stability of proteins is characterized by a subtle balance of into- and inter-molecular interactions. The basic principle of the structure (and of the stability) of the proteins is related to the nature of its normal enviromnent for (water) soluble globular proteins this is the minimization of the hydrophobic surface area, whereas the contrary is the case for membrane proteins (Jaenicke, 1991). 

A basic principle of protein chemistry is the central relationship between three-dimensional structure and activity. Unless the linear polypeptide chain folds into a particular three-dimensional configuration, the protein is inactive. As Fig. 2 illustrates, the active form of a protein is typically a highly convoluted, globular structure in which a particular small domain is the precise locus of interaction with reactant or binding ligand. 

Figure 6.17 Schematic representation of the basic principles of metal chelate affinity chromatography. Certain proteins are retained on the column via the formation of coordinate bonds with the immobilized metal ion (a). The actual structure of the most commonly used metal chelator, iminodiacetic acid, is presented in (b)...

Ras and its relatives are subjects of intensive investigations by biological, biochemical, biophysical, and medical studies. Within just one decade more than 17,000 articles (Medline, 1966-2000) deal with function and properties of this protein. Structural and functional data, based on Ras as a prototype, have provided insight into the basic principles of GTP-binding proteins, their activation, de-activation, and signal transmission. 

In this chapter we introduced some of the basic principles that govern protein structure. The discussion of protein structures begun in this chapter is continued in many other chapters in this text in which we consider structures designed for specific purposes. In chapter 5 we examine the protein structures for two systems the protein that transports oxygen in the blood and the proteins that constitute muscle tissue. In chapters 8 and 9 we discuss structures of specific enzymes. In chapters 17 and 24 we consider proteins that interact with membranes. In chapters 30 and 31 we study regulatory proteins that interact with specific sites on the DNA. And finally, in supplement 3 we examine the structures of immuno-globin molecules. 

The two examples mentioned above illustrated basic principles how protein phosphorylation serves specific biological purposes. Although different kinases might be involved in diverse pathways, the molecular mechanism for the regulation of protein function by phosphorylation is similar By changing protein structure, phosphorylation can turn on/off the catalytic activity of a protein, or create/mask recognition motif for binding by other molecules. 

The work done by Adam Langmuir on monolayers has had many repercussions. Not least was that it was from these two great men that I drew the concepts which enabled me to develop the basic principles of cell membrane structure in the 1930 s. These defined cell membranes has having a lipid bilayer as their continuous phase, sandwiched between two protein layers, and penetrated by hydrophobic proteins. There are now some thousands of biologists studying these membranes, and the source of concepts remains in the work of Adam and Langmuir. I wish we knew as much about the protein components as we do about the lipids. 

After the basic principles of information transfer from genes to proteins had been established with the identification of messenger RNA, the discovery of the medianism of protein synthesis and the structure of genetic code, it was natural for some of us to ask whether the lessons learnt in molecular biology could be applied to the genetics of more complex phenotypes. ... 

FIGURE 3.11 Representation of protein structure showing (a) atomic and (b) spatial arrangement of the helix. (From Roberts, J.D. and Caserio, M.C., Basic Principles of Organic Chemistry, Benjamin Book Publishers, Inc., New York, 1964.)... 

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