Amino acids residues

The secret to the functional diversity of proteins lies partly in the chemical diversity of the amino acids but primarily in the diversity of the three-dimensional structures that these building blocks can form, simply by being linked in different sequences. At the heart of the determination of structure by sequence lie the distinctive characteristics of each of the 20 different amino acids. Table 6.1 shows some general properties of the amino acids along with their three- and one-letter abbreviations. 

Cysteine can bind to either one or two metal ions, and is frequently found as a ligand to iron (e.g., in Fe—S clusters) and to Cu (e.g., in copper chaperones which transfer copper to specific copper-binding proteins). Histidine can bind metal ions in two positions, and has a strong preference for Cu. The 

Biolc ical Inoi anic Chemistry, 2nd Edition. DOI 10.1016 978-0-444-53782-9.00004-8. Copyright 2012 Elsevier B.V. All rights resCTved. 

FIGURE 4.1 Principal protein amino acid side chains involved in metal binding and their metal-ion-binding modes. 

A number of proteins of the blood clotting (coagulation) cascade (including prothrombin, and a number of other clotting factors) undergo post-translational modification in a reaction catalysed by a vitamin K-dependent carboxylase, which transforms specific Glu residues into y-carboxyglutamic acid, Gla (Fig. 4.1). In the reaction (Fig. 4.2), the dihydroquinone (reduced) form of vitamin K, KH2, is oxidised to the epoxide form, KO, by O2. The 

FIGURE 4.2 The vitamin K cycle as it functions in protein glutamyl carboxylation reaction. The conversion of protein-bound glutamic acid into Y-carboxyglutamic acid is catalysed by a carboxylase. During the carboxylation reaction vitamin K hydroquinone (KH2) is converted to vitamin K epoxide (KO). X—(SH)2 and X—S2 represent, respectively, the reduced and oxidised forms of thioredoxin. The NADH-dependent and dithiol-dependent vitamin K reductases are different enzymes. Both the dithiol-dependent K- and KO-reductases are inhibited by dicoumarol (1) and warfarin (11). 

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Proteins consist of large numbers of amino-acids joined by the p>eptide link —CO —NH — into chains, as shown in the diagram, where R and R" are amino-acid residues. These chains are called peptides and may be broken into smaller chains by partial hydrolysis (see peptides). Proteins may contain more than one peptide chain thus insulin consists of... 

Polyethylene (Section 6 21) A polymer of ethylene Polymer (Section 6 21) Large molecule formed by the repeti tive combination of many smaller molecules (monomers) Polymerase chain reaction (Section 28 16) A laboratory method for making multiple copies of DNA Polymerization (Section 6 21) Process by which a polymer is prepared The principal processes include free radical cationic coordination and condensation polymerization Polypeptide (Section 27 1) A polymer made up of many (more than eight to ten) amino acid residues Polypropylene (Section 6 21) A polymer of propene Polysaccharide (Sections 25 1 and 25 15) A carbohydrate that yields many monosacchande units on hydrolysis Potential energy (Section 2 18) The energy a system has ex elusive of Its kinetic energy... 

Alanine (ala) Phenylalanine (phe) R 1 0 - HNCHC N General formula for an amino acid residue Aspartic Acid (asp)... 

Short chains of amino acid residues are known as di-, tri-, tetrapeptide, and so on, but as the number of residues increases the general names oligopeptide and polypeptide are used. When the number of chains grow to hundreds, the name protein is used. There is no definite point at which the name polypeptide is dropped for protein. Twenty common amino acids appear regularly in peptides and proteins of all species. Each has a distinctive side chain (R in Figure 45.3) varying in size, charge, and chemical reactivity. 

Pentapeptide consisting of five amino acid residues (A-E)... 

An alternative approach to peptide sequencing uses a dry method in which the whole sequence is obtained from a mass spectrum, thereby obviating the need for multiple reactions. Mass spec-trometrically, a chain of amino acids breaks down predominantly through cleavage of the amide bonds, similar to the result of chemical hydrolysis. From the mass spectrum, identification of the molecular ion, which gives the total molecular mass, followed by examination of the spectrum for characteristic fragment ions representing successive amino acid residues allows the sequence to be read off in the most favorable cases. 

Two domains, t1 and t2, exist which affect the GR post-DNA binding transcription activity (37). The major (t1) transactivation domain is 185 amino acid residues ia length with a 58-tesidue a-heUcal functional cote (38). The t1 domain is located at the N terminus of the proteia the minor (t2) trans activation domain residues on the carboxy-terminal side of the DNA binding domain. 

KhGH A natural, stmctural variant of hGH called 20-K hGH has been reported to occur in the pituitary as well as in the bloodstream (12,13). This variant, which lacks the 15 amino acid residues from Glu-32 to Gln-46, arises from an alternative splicing of the messenger ribonucleic acid (mRNA) (14). This variant shares many but not all of the biological properties of hGH. 

Fig. 1. Schematic drawing of precursors for selected brain oligopeptides. Shaded areas represent the location of sequences of active peptide products which are normally cleaved by trypsin-like enzymes acting on double-basic amino acid residues. Precursors are not necessarily drawn to scale, (a) CRF precursor (b) proopiomelanocortin (POMC) (c) P-protachykinin (d) proenkephalin A (e) CGRP precursor (f) preprodynorphin, ie, preproenkephalin B. Terms are...

Biosynthesis. Two closely related genes encode the three mammalian tachykinins. The preprotachykinin A gene encodes both substance P and substance K, while the preprotachykinin B gene encodes neuromedin K (45—47). The active sequences are flanked by the usual double-basic amino acid residues, and the carboxy-terrninal amino acid is a glycine residue which is decarboxylated to an amide. As with most neuropeptide precursors, intermediates in peptide processing can be detected, but their biological activities are not clear (ca 1994). 

CGRP has a wide distribution in the nervous system (19) and was the first peptide to be localized to motoneurons (124). It is also found in primary sensory neurons where it is colocalized with substance P (125). CGRP is derived from a precursor stmcturaHy related to the calcitonin precursor. The latter precursor produces two products, calcitonin itself and katacalcin, while the CGRP precursor produces one copy of CGRP (123). Like other peptides, CGRP is cleaved from its precursor by tryptic breakdown between double basic amino acid residues. 

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

Parathyroid hormone, a polypeptide of 83 amino acid residues, mol wt 9500, is produced by the parathyroid glands. Release of PTH is activated by a decrease of blood Ca " to below normal levels. PTH increases blood Ca " concentration by increasing resorption of bone, renal reabsorption of calcium, and absorption of calcium from the intestine. A cAMP mechanism is also involved in the action of PTH. Parathyroid hormone induces formation of 1-hydroxylase in the kidney, requited in formation of the active metabolite of vitamin D (see Vitamins, vitamin d). 

Fig. 7. View of the FeMo-cofactor prosthetic group of the nitrogenase MoFe protein with some of the surrounding amino acid residues where ( ) represents the molybdenum coordinated to a-His-442 and homocitrate (at the top), ( ) represents the iron, interspersed with the sulfur (O) and carbon...

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