Amino acid structures

Figure 1.1 The amino acid sequence of a protein s polypeptide chain is called Its primary structure. Different regions of the sequence form local regular secondary structures, such as alpha (a) helices or beta (P) strands. The tertiary structure is formed by packing such structural elements into one or several compact globular units called domains. The final protein may contain several polypeptide chains arranged in a quaternary structure. By formation of such tertiary and quaternary structure amino acids far apart In the sequence are brought close together in three dimensions to form a functional region, an active site.

The number and order of all of the amino acid residues in a polypeptide constitute its primary structure. Amino acids present in peptides are called aminoacyl residues and are named by replacing the -au or -ine suffixes of free amino acids with -yl (eg, alany/, asparg//, ty-... 

Fig. 2 Illustration of protein structure levels. Shown are primary structure (amino acid sequence), secondary structure (local order of protein chain, a-helix shown as an example), tertiary structure (assembly of secondary structure elements), and quaternary structure (relationship of different protein chain in multisubunit protein). (From Ref. 66.)...

Thus far we have concentrated on the primary structure (amino acid sequence) of a polypeptide. Higher level protein structure can be described at various levels, i.e. secondary, tertiary and quaternary ... 

In addition to their well known role in protein structure, amino acids also act as precursors to a number of other important biological molecules. For example, the synthesis of haem (see also Section 5.3.1), which occurs in, among other tissues, the liver begins with glycine and succinyl-CoA. The amino acid tyrosine which maybe produced in the liver from metabolism of phenylalanine is the precursor of thyroid hormones, melanin, adrenaline (epinephrine), noradrenaline (norepinephrine) and dopamine. The biosynthesis of some of these signalling molecules is described in Section 4.4. 

Primary structure (amino acid sequence in a polypeptide chain)... 

Reducing agents Proteins of structure (amino acids)... 

FIGURE 4-20 Stable folding patterns in proteins, (a) Two simple and common motifs that provide two layers of secondary structure. Amino acid side chains at the interface between elements of secondary structure are shielded from water. Note that the f) strands in the loop... 

Fig. 8. The four levels of structure in proteins, (a) Primary structure (amino acid sequence), (b) secondary structure (a-helix), (c) tertiary structure, (d) quaternary structure.

There are different classes of protein sequence databases. Primary and secondary databases are used to address different aspects of sequence analysis. Composite databases amalgamate a variety of different primary sources to facilitate sequence searching efficiently. The primary structure (amino acid sequence) of a protein is stored in primary databases as linear alphabets that represent the constituent residues. The secondary structure of a protein corresponding to region of local regularity (e.g., a-helices, /1-strands, and turns), which in sequence alignments are often apparent as conserved motifs, is stored in secondary databases as patterns. The tertiary structure of a protein derived from the packing of its secondary structural elements which may form folds and domains is stored in structure databases as sets of atomic coordinates. Some of the most important protein sequence databases are PIR (Protein Information Resource), SWISS-PROT (at EBI and ExPASy), MIPS (Munich Information Center for Protein Sequences), JIPID (Japanese International Protein Sequence Database), and TrEMBL (at EBI). ... 

Schier R, Balint RF, McCall A, Apell G, Larrick JW, Marks JD, Identification of functional and structural amino-acid residues by parsimonious mutagenesis, Gene, 169 147-155, 1996. 

Primary structure Amino acid sequencing, N-terminal Edman sequencing, peptide mapping... 

Since that time many more sequences have become available through the advent of recombinant DNA technology and the deduction of amino acid sequences from the base sequences of cloned DNA. At the present time, the primary structures (amino acid sequences) of 14 proteins of the transferrin family have been established. These include seven serum transferrins, from human 10, 36), pig (37), horse 38), rabbit 39), toad Xenopus laevis) 40), sphinx moth (M. sexta) 13), and cockroach Blaberus discoidalis 4) chicken 34, 35) and duck 41) ovotransfer-rins four lactoferrins, from human (11, 42), mouse 43), pig 44) and cattle 45, 46) and the human tumor cell melanotransferrin 47). All of these sequences are available from sequence databases such as EMBL and SWISSPROT. 

This technique has been successfully applied in those biological targets where the key structural amino acids of the native peptide for peptide recognition are known. Miscellaneous examples are found in glycoprotein Gbllb/IIIa inhibitors (33)that mimic the RGD sequence (64) or in Ras-farnesyltransferase inhibitors (34) that mimic the CAAX sequence (Fig. 15.15) (65). 

Primary Structure Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains... 

The biosynthesis of the adenine nucleotide carrier has been studied most extensively in Neurospora crassa. The carrier isolated from Neurospora mitochondria is very similar to the carrier isolated from mammalian mitochondria [78]. Its molecular weight, subunit structure, amino acid composition, hydrophobicity and inhibitor specificity are remarkably similar to the mammalian heart and liver carriers. Specific antibodies to the Neurospora carrier have been raised in rabbits [79]. 

Les.), and Couceiro, de Almeida, and Freire (1953) have localized it histo-chemically in the electrical tissue of Electwphorus electricus L. The distribution of carbonic anhydrase in several tissues of two teleosts and its inhibition in vivo by the sulfonamides have been investigated by Maetz (1953a,b). The presence of cathepsin in the stomachs of various animals including pike and trout has been established by Buchs (1954). A new advance has also been made in the comparative study of pepsin. This enzyme, previously crystallized from salmon (Norris and Elam, 1940), halibut (Eriksen, 1943), and shark (Sprissler, 1942), has now been crystallized from three species of tuna (Norris and Mathies, 1953). These interesting researches have shown that fish pepsins differ in crystal structure, amino acid composition, and specificity from swine or bovine pepsins and show a closer relationship to one another. As pointed out by Velick and Udenfriend (1953), specificity requirements toward substrates are less exacting with extracellular enzymes. 

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