Polypeptide chains and

Through combined effects of noncovalent forces, proteins fold into secondary stmctures, and hence a tertiary stmcture that defines the native state or conformation of a protein. The native state is then that three-dimensional arrangement of the polypeptide chain and amino acid side chains that best facihtates the biological activity of a protein, at the same time providing stmctural stabiUty. Through protein engineering subde adjustments in the stmcture of the protein can be made that can dramatically alter its function or stabiUty. 

Figure 6.25 Schematic diagram of the structure of one dimer of phosphofructokinase. Each polypeptide chain is folded Into two domains (blue and red, and green and brown), each of which has an oi/p structure. Helices are labeled A to M and p strands 1 to 11 from the amino terminus of one polypeptide chain, and respectively from A to M and 1 to 11 for the second polypeptide chain. The binding sites of substrate and effector molecules are schematically marked In gray. The effector site of one subunit is linked to the active site of the other subunit of the dimer through the 6-F loop between helix F and strand 6. (Adapted from T. Schlrmer and P.R. Evans, Nature 343 140-145, 1990.)...

The bacterial photosynthetic reaction center is built up from four different polypeptide chains and many pigments... 

From a map at low resolution (5 A or higher) one can obtain the shape of the molecule and sometimes identify a-helical regions as rods of electron density. At medium resolution (around 3 A) it is usually possible to trace the path of the polypeptide chain and to fit a known amino acid sequence into the map. At this resolution it should be possible to distinguish the density of an alanine side chain from that of a leucine, whereas at 4 A resolution there is little side chain detail. Gross features of functionally important aspects of a structure usually can be deduced at 3 A resolution, including the identification of active-site residues. At 2 A resolution details are sufficiently well resolved in the map to decide between a leucine and an isoleucine side chain, and at 1 A resolution one sees atoms as discrete balls of density. However, the structures of only a few small proteins have been determined to such high resolution. 

The ion pore has a narrow ion selectivity filter The bacterial photosynthetic reaction center is built up from four different polypeptide chains and many pigments The L, M, and H subunits have transmembrane a helices... 

FIGURE 6.27 The natural right-handed twist exhibited by polypeptide chains, and the variety of structures that arise from this twist. 

In the unfolded state, the peptide chain and its R groups interact with solvent water, and any measurement of the free energy change upon folding must consider contributions to the enthalpy change (AH) and the entropy change (A.S) both for the polypeptide chain and for the solvent ... 

Transfer RNA (tRNA) serves as a carrier of amino acid residues for protein synthesis. Transfer RNA molecules also fold into a characteristic secondary structure (marginal figure). The amino acid is attached as an aminoacyl ester to the 3 -terminus of the tRNA. Aminoacyl-tRNAs are the substrates for protein biosynthesis. The tRNAs are the smallest RNAs (size range—23 to 30 kD) and contain 73 to 94 residues, a substantial number of which are methylated or otherwise unusually modified. Transfer RNA derives its name from its role as the carrier of amino acids during the process of protein synthesis (see Chapters 32 and 33). Each of the 20 amino acids of proteins has at least one unique tRNA species dedicated to chauffeuring its delivery to ribosomes for insertion into growing polypeptide chains, and some amino acids are served by several tRNAs. For example, five different tRNAs act in the transfer of leucine into... 

PDGF Isoforms consist of homo- and heterodimers of A- and B-polypeptide chains and homodimers of C- and D-polypeptide chains PDGFR Consists of PDGFR a and (3 receptors Embryonic development, particularly in the formation of the kidney, blood vessels, and various mesenchymal tissues. Proliferation of connective tissues, glial and smooth muscle cells... 

FIGURE 19.19 A representation of part of an a helix, one of the secondary structures adopted by polypeptide chains. The cylinder encloses the "backbone" of the polypeptide chain, and the side groups project outward from it. The thin lines represent the hydrogen bonds that maintain the helical shape. 

Edman degradation A method of amino acid sequencing in proteins in which successive V-terminal amino acids are removed from the polypeptide chain and identified. 

Based on the nature of the linkage between their polypeptide chains and their oligosaccharide chains, glycoproteins can be divided into three major classes (Figure 47-1) (1) those containing an O-glycosidic linkage (ie,... 

The transglutaminases are calcium-dependent enzymes that catalyse the cross-linking of proteins by promoting the formation of isopeptide bonds between the /-carboxyl group of a glutamine in one polypeptide chain and the e-amino group of a lysine in the second (Greenberg et al., 1991). These... 

Edelman, G.M., Gall, W.E., Waxdal, M.J., and Konigsberg, W.H. (1968) The covalent structure of a human gG-immunoglobulin. I. Isolation and characterization of the whole molecules, the polypeptide chains, and the tryptic fragments. Biochemistry 7, 1950-1958. 

The folding of polypeptide chains and the assembly of multiple subunits are critical requirements when complex and multimeric proteins such as full size antibodies... 

Table 2.1 Selected examples of proteins. The number of polypeptide chains and amino acid residues constituting the protein are listed, along with its molecular mass and biological function...

The polymer level is reached with the polypeptide chain, a long (usually 20+) chain of amino acids. A protein consists of one or more polypeptide chains. For proteins with only one chain, the chain is the protein. For multiple-chain proteins, known as oligomeric proteins, the polypeptide chain and protein levels must be viewed separately. Each different polypeptide chain has its own unique primary structure. 

Many protein molecules are composed of more than one subunit, where each subunit is a separate polypeptide chain and can form a stable folded structure by itself. The amino acid sequences can either be identical for each subunit (as in tobacco mosaic virus protein), or similar (as in the a and )3 chains of hemoglobin), or completely different (as in aspartate transcarbamylase). The assembly of many identical subunits provides a very efficient way of constructing... 

Many proteins are synthesized in inactive forms, termed proproteins. Insulin is created as an inactive single polypeptide chain and must be cleaved to create the active hormone. Many proteolytic enzymes are made as inactive precursors and must be cleaved to form enzymatically active molecules. 

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