Amino acids internal sequencing

EXON The portion of a gene that contains the amino acid coding sequences and that remains represented in mature mRNA after mRNA precursors have been spliced to remove internal noncoding regions (i.e., introns). 

Proteins are linear polymers of amino acids. The sequence of a protein s constituent amino acids determines its biochemical function. The mRNA sequence is read in groups of three, called codons. Because there are four bases in DNA or RNA, there are 64 (4 ) codons. Only 20 amino acids are specified by translation, so there is more than one codon per amino acid. In other words, the genetic code is redundant. The code also contains punctuation marks. Three codons, UAG, UAA, and UGA, specify stop signals (like the periods in a sentence). One amino acid, methionine, coded by AUG, is used to initiate each protein (like a capital letter at the beginning of a sentence). Just as a letter that starts a sentence can also appear in an uncapitalized form inside the sentence, so methionine also appears internally in proteins. See Table 4-1. 

Ellipsoidal and spherical shape are especially prevalent among proteins, which are naturally occurring copolymers of a-amino acids. Certain sequences of these a-amino acids are helical, whereas others are not (Figure 4-14). The interaction of these ordered and disordered conformational sequences with each other and with the solvent thus determine the internal structure and external shape. In water, for example, hydrophilic groups will tend to occupy positions on the surface of the protein, and hydrophobic groups will tend towards the interior. With myoglobin, for example, only two amino acid residues with hydrophilic substituents are to be encountered in the protein interior. Such a protein molecule, then, will appear as a quite compact sphere or as an ellipsoid. 

Enzymes are excellent catalysts for two reasons great specificity and high turnover rates. With but few exceptions, all reac tions in biological systems are catalyzed by enzymes, and each enzyme usually catalyzes only one reaction. For most of the important enzymes and other proteins, the amino-acid sequences and three-dimensional structures have been determined. When the molecular struc ture of an enzyme is known, a precise molecular weight could be used to state concentration in molar units. However, the amount is usually expressed in terms of catalytic activity because some of the enzyme may be denatured or otherwise inactive. An international unit (lU) of an enzyme is defined as the amount capable of producing one micromole of its reaction product in one minute under its optimal (or some defined) reaction conditions. Specific activity, the activity per unit mass, is an index of enzyme purity. 

Since the outside of the barrel faces hydrophobic lipids of the membrane and the inside forms the solvent-exposed channel, one would expect the P strands to contain alternating hydrophobic and hydrophilic side chains. This requirement is not strict, however, because internal residues can be hydrophobic if they are in contact with hydrophobic residues from loop regions. The prediction of transmembrane p strands from amino acid sequences is therefore more difficult and less reliable than the prediction of transmembrane a helices. 

Several splice variants of MOP (formerly MOR-1) have been cloned (MOP-1A to MOR-1X). The B, C, andD variants differ in their amino acid sequence at the C-terminal end [4]. These receptor valiants differ in their distribution in the central nervous system and in the rate of internalization and desensitization upon... 

The amino acid sequence of our first aPNA (which we termed backbone 1 or bl) was designed based on this amphipathic hehx sequence (Fig. 5.3 B). Specifically, this aPNA backbone included hydrophobic amino acids (Ala and Aib), internal salt bridges (Glu-(aa)3-Lys-(aa)3-Glu), a macrodipole (Asp-(aa)i5-Lys), and an N-ace-tyl cap to favor a-helix formation. The C-termini of these aPNA modules end in a carboxamide function to preclude any potential intramolecular end effects. Each aPNA module incorporates five nucleobases for Watson-Crick base pairing to a target nucleic acid sequence. 

Fig. 3. (A) Model of the proposed pore forming part of K channel subunits. Segments S5 and S6 are possibly membrane-spanning helices. The helices are connected by a hydrophobic segment H5 which may be tucked into the lipid bilayer [48]. H5 is flanked by two proline residues P. Adjacent to these proline residues are amino acid side chains ( ) important for external TEA binding [45,46]. Approximately halfway between these two proline residues are amino acid side chains ( ) affecting internal TEA binding [46,47] and K channel selectivity [48]. (B) Mutations are indicated which affect in Shaker channels external TEA (TEAe) or internal TEA (TEA,) binding. Concentrations of TEA for half block of the wild-type and mutant K channels are given at the right-hand side of the corresponding sequence. Data have been compiled from [45-47].

Determination of the amino-acid sequence of human serum transferrin (MacGillivray et ah, 1983) and of human lactoferrin (Metz-Boutique etal., 1984) revealed an internal two-fold sequence repeat. The amino-terminal half has approximately 40 % sequence identity with the carboxyl-terminal half. Similar results have subsequently been found for a number of other transferrins (Baldwin,... 

Major differences in the amino acid sequences of the intracellular domains of the opiate receptors reside in the C-terminal tail [8]. While this domain is not essential for coupling to G proteins it may be important for the desensitization and internalization of the opiate receptors. 

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