Primary Structures of Proteins

The 20 a-amino acids found in most proteins. The R group is shown in color. 

How does the nature of the side chain affect the three dimensionai structure of a protein  

The protein polymer is built by reactions between amino acids. For example, two amino acids can react as follows, forming a C—N bond wifh fhe elimination of water. 

The product shown is called a dipeptide. The term peptide comes from the structure 

The 20 amino acids can be assembled in any order, which makes possible an enormous number of different proteins. This variety allows for the many types of proteins needed for the functions that organisms carry out. 

The amino acid sequence (the primary structure) of a protein determines its three-dimensional structure, which, in turn, determines its properties. In every protein, the correct three-dimensional structure is needed for correct functioning. 

Determining the sequence of amino acids in a protein is a routine, but not trivial, operation in classical biochemistry. It consists of several steps, which must be carried out carefully to obtain accurate results (Section 5.4). 

The following Biochemical Connections box describes an important practical aspect of the amino acid composition of proteins. This property can differ markedly, depending on the source of the protein (plant or animal), with important consequences for human nutrition. 

The primary structure of a protein determines the other levels of structure. A single amino acid substitution can give rise to a malfunctioning protein, as is the case with sickle-cell anemia. 

It is the sequence of amino acids that constitutes the primary structure of a protein. This in turn determines the way a protein folds and assumes the 

1 Determination of Amino acid Sequence from DNA sequence. Understanding genetic codes and our ability to sequence nucleotides in a DNA segment made it possible to decipher the amino acid sequence of a protein encoded by a gene. It became customary to infer the amino acid sequences of different proteins as soon as the DNA sequence data became available in the gene bank. The primary structure of a large number of proteins deposited in the protein data bank (PDB) is obtained directly from the DNA sequence data. 

When the methodology of 2D gel for separation of proteins became available in the mid-1970s, the proteins separated by 2D gel were routinely subjected to Edman degradation to determine the amino acid sequence, because this was the only way to determine amino acid sequence of a protein at that time. However, there are two problems with this approach in proteomics First, many proteins possess N-terminal proteins that are blocked and therefore cannot react with the phenylisothiocynate required for Edman degradation. Second, Edman degradation can determine the amino acid sequence of one protein at a time, which is contrary to the objectives of proteomics that aim at gaining the information of several proteins at the same time. 

2 Proteomics Based on Mass Spectrometry —Identification of Proteins Based on Their Amino Acid Sequence 

3 Components of the Instrument. A spectrometer consists of the following five major components a port or device for the introduction of 

A peptide chain has an amino acid with the free (without a peptide bond) amino group on one end (the N-terminal end), and an amino acid with free (without a peptide bond) carboxylic group on the other end (the C-terminal end). 

In Chapter 20 we saw that many useful synthetic materials are polymers. A great many natural materials are also polymers starch, hair, silk and cotton fibers, and the celluiose in woody plants, to name only a few. 

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The amino acid sequences in (a) oxytocin and (b) vasopressin. The differing amino acids are enclosed in boxes. 

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FIGURE 5.8 Two structural motifs that arrange the primary structure of proteins into a higher level of organization predominate in proteins the a-helix and the /3-pleated strand. Atomic representations of these secondary structures are shown here, along with the symbols used by structural chemists to represent them the flat, helical ribbon for the a-helix and the flat, wide arrow for /3-structures. Both of these structures owe their stability to the formation of hydrogen bonds between N—H and 0=C functions along the polypeptide backbone (see Chapter 6). 

A new chapter on the primary structure of proteins, which provides coverage of both classic and newly emerging proteomic and genomic methods for identifying proteins. A new section on the appHcation of mass spectrometry to the analysis of protein structure has been added, including comments on the identification of covalent modifications. 

Pellequer, J. L., Westhof, E. andVanRegenmortel, M. H. V. (1994), Epitope prediction from primary structure of proteins , in G. B. Wisdom (Ed.), Peptide Antigens A Practical Approach, IRL Press, Oxford, UK, pp. 7-25. 

Historically, data on primary structures of proteins were used to help establish evolutionary relationships between organisms by reversing the following sequence ... 

Dr Bhushan has a research experience of 41 years. He received prestigious Alexander von Humboldt fellowship of Germany in the year 1988, and worked for research at the University of Oldenburg, and at the University of Giessen, Germany. He received European Economic Community Fellowship in 1992 and worked at University of Bristol, UK, on Rye protein. He is an elected Fellow of the Royal Society of Chemistry, London (including Chartered Chemist). He also worked on establishment of primary structures of proteins of Peanut, Brassica, and Soybean, and published several research papers from Univ of Roorkee. He also worked as post doc fellow at the Washington State University, USA. 

The primary structure of proteins is not the whole story. To really understand how proteins work, we have got to understand them as three-dimensional objects. So on to higher dimensions in the next chapter. But first, a few paragraphs about another role for the protein amino acids biosynthesis. 

The primary structure of proteins determines the three-dimensional or tertiary structure. 

In all living cells, DNA serves to store genetic information. Specific segments of DNA ( genes ) are transcribed as needed into RNAs, which either carry out structural or catalytic tasks themselves or provide the basis for synthesizing proteins (see p.82). In the latter case, the DNA codes for the primary structure of proteins. The language used in this process has four letters (A, G, C, and T). All of the words ( codons ) contain three letters ( triplets ), and each triplet stands for one of the 20 proteinogenic amino acids. 

Like all fats, milk fat provides lubrication. They impart a creamy-mouth feel as opposed to a dry texture. Fat globules produce a shortening effect in cheese by keeping the protein matrix extended to give a soft texture. Milk proteins are one of the most important constituents. The primary structure of proteins consists of... 

P. J. Parker, L. Coussens, N. Totty, L. Rhea, S. Young, E. Chen, S. Stabel, M. D. Waterfield, A. Ullrich (1986). The complete primary structure of protein kinase C, the major phorbol ester receptor. Science 233 853-859. 

The sequence of amino acids in a protein is called the primary struc ture of the protein. Understanding the primary structure of proteins is important because many genetic diseases result in proteins with abnor mal amino acid sequences, which cause improper folding and loss or impairment of normal function. If the primary structures of the normal and the mutated proteins are known, this information may be used to diagnose or study the disease. 

W. A. Schroeder, The Primary Structures of Proteins, Harper and Row, New York, 1968. 

The amino-acids that make up the primary structure of proteins will change their charge when the pH of the solution is altered due to their acid-base properties (Section 5.3 and Appendix 5.1). The effects of pH on enzyme-catalysed reactions can be complex since both Km and may be affected. Here, only the effects on Kmax are considered, as this usually reflects a single constant rather than several that may be associated within the constant Km (see Section 5.4.4.). It is assumed that pH does not change the limiting step in a multi-step process and that the substrate is saturating at all times. 

The a-aminocarboxylic acids are of particular importance as the result of their involvement in the primary structure of protein molecules. Although customarily represented by the general formula NHj CHR-CC H amino acids are... 

Primary Structure of Proteins The primary structure of a protein is the sequence of amino acids in the peptide chain. The primary structure is immensely important, because it is the sequence of amino acids that determines the higher levels of protein structure and, consequently, the function of the protein. Small changes in the primary structure can cause a protein to be completely nonfunctional. For example, sickle cell anemia is caused by the substitution of a single amino acid in the hemoglobin chain. 

Stereochemistry of Amino Acids 339 Acid-Base Properties of Amino Acids 339 The Isoelectric Point 342 Electrophoresis 343 The Peptide Bond 343 Primary Structure of Proteins 344 Secondary Structure of Proteins 344 Tertiary Structure of Proteins 345 The Folding Problem 346 Denaturing Proteins 346 Enzymes 347... 

While the primary structure of proteins and nucleic acids can be experimentally determined in a straight-forward manner, their higher-order structures are much more difficult to elucidate. In general, computational methods dealing with primary structure focus on interpretation of the structure-function, as in promoter analysis. By contrast computational methods working on higher-order structure instead focus on the prediction of structural details. Further, most techniques are limited to the prediction of RNA and protein structures—sugar-, fatty-add-, and DNA-structural prediction methods are in their infancy. 

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