Structure proteins, basic principles

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. 

Two basic principles govern the arrangement of protein subunits within the shells of spherical viruses. The first is specificity subunits must recognize each other with precision to form an exact interface of noncovalent interactions because virus particles assemble spontaneously from their individual components. The second principle is genetic economy the shell is built up from many copies of a few kinds of subunits. These principles together imply symmetry specific, repeated bonding patterns of identical building blocks lead to a symmetric final structure. 

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. 

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). 

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. 

Aconitase was the first protein to be identified as containing a catalytic iron-sulfur cluster [24-26]. It was also readily established that the redox properties of the [4Fe-4S](2+ 1+) cluster do not play a role of significance in biological functioning the 1 + oxidation state has some 30% of the activity of the 2+ state [25], Since then several other enzymes have been identified or proposed to be nonredox iron-sulfur catalysts. They are listed in Table 2. It appears that all are involved in stereospecific hydration reactions. However, these proteins are considerably less well characterized than aconitase. In particular, no crystal structural information is available yet. Therefore, later we summarize structural and mechanistic information on aconitase, noting that many of the basic principles are expected to be relevant to the other enzymes of Table 2. 

To a newcomer to the technique, once you have gotten over the disappointment of its relative insensitivity and you have invested a little time and effort in understanding the basic principles, you cannot fail to be impressed by its power and versatility. NMR will inevitably have applications in your field of study, whether it is structure determination on your favorite protein or peptide or measurements on the intact biological system in which it functions. 

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. 

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. 

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