Tertiary Structure of Peptides and Proteins

Intelligent Design in Combinatorial Chemistry Use of Designed Peptide Libraries to Explore Secondary and Tertiary Structures in Peptides and Proteins... 

In the remainder of this chapter, we will describe the main features of peptide and protein structure. We will first examine what is called the primary structure of peptides and proteins that is, how many amino acids are present and what their sequence is in the peptide or protein chain. We will then examine three-dimensional aspects of peptide and protein structure, usually referred to as their secondary, tertiary, and quaternary structures. 

However, 2D NOE studies are invaluable in structure determination, in particular of peptides and proteins here the NOEs give invaluable information for conformational analysis and the determination of the tertiary structures of proteins. 

The biological function of peptides and proteins depends on their native conformation. The side-chain functionalities of the a-amino acids that comprise peptides and proteins have profound effects on their properties. These functionalities reside in the 20 naturally occurring a-amino acids, which have different propensities for formation of the three major secondary structural conformations. 1 In addition to these naturally occurring a-amino acids whose primary structure enables the polypeptide to fold into a predictable secondary and tertiary structure, the incorporation of unnatural amino acids has opened important areas of research. 

Hydrophobicity is a property shared to varying degrees by most proteins and is imparted primarily through the side chains of neutral aromatic amino acids phenylalanine, tyrosine and tryptophan. By their lower attraction for water molecules, these amino acids tend to link to one another, thus expelling water from the molecule. While hydrophobicity is one of the natural forces that confer stability on the tertiary structure of peptides, it also imparts stability to formed immune complexes and depending on environmental factors, can exist also between different protein molecules. 

H. Kawai, T. Kikuchi, and Y. Okamoto, Protein Engin., 3, 85 (1989). A Prediction of Tertiary Structures of Peptide by the Monte Carlo Simulated Annealing Method. 

The peptide (amide) linkages of peptides and proteins can be hydrolyzed under appropriate conditions. This destroys the primary structure and produces smaller peptides or amino acids. The characteristic secondary, tertiary, and quaternary structures of proteins can also be disrupted by certain physical or chemical conditions such as extreme temperatures or pH values. The disruption of these structures is called denaturation and causes the protein to become nonfunctional and, in some cases, to precipitate. 

The tertiary structure of the final protein begins to appear during P.b., before completion of the polypeptide. In many cases, the protein is subjected to further reactions, which convert it into its biologically active form, e.g. by covalent attachment of certain groups, or by removal of certain sequences of amino acids (see Post-translational modification of proteins). The initial translation product of secretory proteins contains a metabolically short-lived N-terminal peptide sequence, which functions in the attachment of the ribosome to the membrane of the rough endoplasmic reticulum and in the transfer of these proteins across the membrane into the tubules of the endoplasmic reticulum (see Signal hypothesis). 

When one computes the amino acid substitution observed in protein of spontaneous or experimental TMV mutants, almost all the tryptic polypeptides clearly are subject to substitution except one—peptide IX. Changes in the tertiary structure of peptide IX are fatal to the protein configuration and prevent reaggregation of the RNA and virus protein. Uncoated RNA is rapidly digested by hydrolases. 

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