Conformation of a polypeptide

The secondary structure of a protein is the shape adopted by the polypeptide chain—in particular, how it coils or forms sheets. The order of the amino acids in the chain controls the secondary structure, because their intermolecular forces hold the chains together. The most common secondary structure in animal proteins is the a helix, a helical conformation of a polypeptide chain held in place by hydrogen bonds between residues (Fig. 19.19). One alternative secondary structure is the P sheet, which is characteristic of the protein that we know as silk. In silk, protein... 

The term tertiary stmcmre refers to the entire three-dimensional conformation of a polypeptide. It indicates, in three-dimensional space, how secondary stmcmral feamres—hehces, sheets, bends, mrns, and loops— assemble to form domains and how these domains relate spatially to one another. A domain is a section of protein strucmre sufficient to perform a particular chemical or physical task such as binding of a substrate... 

Secondary structure can be described as the local spatial conformation of a polypeptide s backbone, excluding the constituent amino acid s side chains. The major elements of secondary structure are the a-helix and P-strands, as described below. 

Statistical averages of various physical quantities characterizing the conformation of a polypeptide chain under given environmental conditions can be calculated with the help of Eq. (B-6). For example, the average helical fraction fN (in what follows, this is simply called helical fraction) is given by... 

From the above discussion it is clear that the average conformation of a polypeptide in solution depends on both the chain length N and the co-operativity parameter a, even if the helical fraction is fixed. In particular, it has been shown that, when compared at the same fN and N, the average number of helical sequences, gN, becomes smaller as a is lowered. Thus for fixed fN and N there exist a variety of different interrupted helical conformations, depending on the magnitude of a. Figure 4 illustrates two typical examples of such conformations. This theoretical prediction makes a study of the conformation-dependent properties of synthetic polypeptides rather inviting. 

In Chapter B it has been shown that, if the restrictions that N> 1, a112 < 1, and No112 > 2 are imposed, very useful approximate expressions can be derived for the quantities characterizing the average conformation of a polypeptide molecule. Teramoto et al. (i4) have simplified Nagai s expressions for by imposing the same restrictions. Their results read... 

An especially favorable conformation of a polypeptide chain that was originally deduced by Pauling and Corey is the alpha helix (Figure 25-11). The principal feature of the a helix is the coiling of the polypeptide chain in... 

Typically, proteins fold to organize a very specific globular conformation, known as the protein s native state, which is in general reasonably stable and unique. It is this well-defined three-dimensional conformation of a polypeptide chain that determines the macroscopic properties and function of a protein. The folding mechanism and biological functionality are directly related to the polypeptide sequence a completely random amino acid sequence is unlikely to form a functional structure. In this view, polypeptide sequence... 

A protein is a linear sequence of amino acids linked together by peptide bonds. The peptide bond is a covalent bond between the oi-amino group of one amino acid and the a-carboxyl group of another. The peptide bond has partial double bond character and is nearly always in the trans configuration. The backbone conformation of a polypeptide is specified by the rotation angles about the Ca-N bond phi, (j>) and Ca-C bond psi, amino acid residues. The sterically allowed values of 0 and yr are visualized in a Ramachandran plot. When two amino acids are joined by a peptide bond they form a dipeptide. Addition of further amino acids results in long chains called oligopeptides and polypeptides. 

G. Nemethy and H. A. Scheraga, Biopolymers, 3,155 (1965). Theoretical Determination of Sterically Allowed Conformations of a Polypeptide Chain by a Computer Method. 

G. H. Paine and H. A. Scheraga, Biopolymers, 24, 1391 (1985). Prediction of the Native Conformation of a Polypeptide by a Statistical-Mechanical Procedure. 1. Backbone Structure of Enkephalin. 

Paine GH, Scheraga HA (1986) Prediction of the native conformation of a polypeptide by a statistical mechanical procedure II. Average backbone structure of enkephalin. Biopolymers 25 1547-1563... 

The two important kinds of conformation of a polypeptide chain are the helix and the random coil. In the helical form, the amide hydrogen of each amide group, ... 

Two attempts have been reported to predict the conformation of a polypeptide hormone by assembling the appropriate residues in their predicted conformation (63, 90). In this manner, the amino acid sequence of bradykinin was predicted to exist in a random coil conformation, with variation around the glycine bond, and with no interaction predicted between phenyl groups. As yet no experimental evidence confirms this prediction however, existing experimental evidence suggests that the prediction is reasonable (67-69). In the second study the conformation of gastrin tetrapeptide was predicted (90). 

We have already discussed primary structure in terms of the general character of amino acids and some specific examples of amino acid sequences in certain proteins will be discussed later. Our attention now is focused on secondary structure, or conformation as we called it when we discussed synthetic polymers. There are a number of factors that afreet the conformation of a polypeptide chain and a lot can be learned initially by just focusing on two of these steric restrictions on bond rotations and the strong driving force for amide groups to hydrogen bond to one another. 

The aim of this final section is twofold. It will first examine the basis upon which the rotatory dispersions of proteins may be treated in the same manner that has been employed for synthetic polypeptides and, secondly, assess the extent to which the dispersive properties of proteins may be quantitatively explained in terms of known conformations of a polypeptide chain. A pattern of conformational analysis embodying the hypothesis that a polypeptide chain is partitioned into standard helical segments and disordered regions has been shown capable of a rather precise estimate of partial helical content in polymers such as poly-L-lysine and copoly-L-... 

Pauling and Corey predicted the structure of the a helix 6 years before it was actually seen in the x-ray reconstruction of the structure of myoglobin. The elucidation of the structure of the a helix is a landmark in biochemistry because it demonstrated that the conformation of a polypeptide chain can be predicted if the properties of its components are... 

Computer simulation of biomolecules in aqueous solution is challenging, even for small molecules such as peptides. In principle, in order to fully characterise its folding or binding properties, one would like to compute the complete ensemble of conformations of a polypeptide in solution as a function of time. This, however, becomes an extremely complex problem as soon as one wishes to use an accurate energy function and model all the degrees of freedom that describe the polypeptide chain and the solvent. 

Alpha helix. A helical conformation of a polypeptide chain, predominantly right-handed, with maximal intrachain hydrogen bonding of the peptide bonds one of the most common secondary structures in proteins. 

Alteration of the specific native conformation of a polypeptide chain, protein, or nucleic acid. See degradation. 

A solid-state NMR technique for the determination of peptide backbone conformations at specific sites in unoriented samples under MAS has been described and demonstrated on labeled samples of tripeptide AlaClyGly and 17-residue peptide. Experiments and simulations show that both c ) and xj/ backbone dihedral angles can be extracted from a single data set. This technique, called DQCSA spectroscopy, may be especially useful when analyzing the backbone conformation of a polypeptide at a particular doubly labeled site in the presence of additional labeled carbons along the sequence. 

Proteins contain many single bonds capable of free rotation. Theoretically, therefore, proteins can assume an infinite number of possible conformations but under normal biological conditions, they assume only one or a very small number of most stable conformations. Proteins depend upon these stable conformations for their specific biological functions. A functional protein is said to be in its native form, usually the most stable one. The three-dimensional conformation of a polypeptide chain is ultimately determined by its amino acid sequence (primary structure). Changes in that sequence, as they arise from mutations in DNA, may yield conformationally altered (and often less stable, less active, or inactive) proteins. Since the biological function of a protein depends on a... 

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