Amino acid sequence, effect

Where Kunf and Kfiuct are the equilibrium constants for the unfolding transitions and fluctuations respectively. For simplicity, both the unfolded and the fluctuated conformations are assumed to exchange with the rate determined from unstructured dipeptides (Bai et al., 1993 Connelly et al., 1993). This may be a poor assumption, especially for the fluctuated form, but it allows the rates to be normalized for temperature, pH and amino acid sequence effects. Kpp, the equilibrium constant determined from kobs / is then given by... 

L-alanine content (between 20 and 30%), any significant changes in chemical shift change was observed for chemical shift changes may be mainly due to the side-chain effect of the L-valine residue and the neighbouring amino acid sequence effects, but apparently are not due to the main-chain conformation of copolypeptides. 

For a series of [Ala, Asp(OBzl)] , the value of a22 decreases linearly as the L-alanine content increases (5 20% of the L-alanine content). This change of the 022 value may be due mainly to neighbouring amino acid sequence effects, but not to the main-chain conformation of polypeptides. The a[SO, ox, and <733 values, on the other hand, do not change at this L-alanine content (5 20%). 

Figures 27 and 28 show the plots of aiso, au, a22, and o33 values of various [Gly, Ala] and [Gly, Leu] against glycine content. It is interesting that the value of <7iso is nearly constant, but the principal shielding tensor components are displaced over a wide range of glycine content (20 100%). Therefore, these tensor components contain some information about neighbouring amino acid sequence effects as well as conformation. The reason for this is not clear at present.

Given a large population of individuals, a considerable number of sequence variants can be found for a protein. These variants are a consequence of mutations in a gene (base substitutions in DNA) that have arisen naturally within the population. Gene mutations lead to mutant forms of the protein in which the amino acid sequence is altered at one or more positions. Many of these mutant forms are neutral in that the functional properties of the protein are unaffected by the amino acid substitution. Others may be nonfunctional (if loss of function is not lethal to the individual), and still others may display a range of aberrations between these two extremes. The severity of the effects on function depends on the nature of the amino acid substitution and its role in the protein. These conclusions are exemplified by the more than 300 human... 

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. 

The removal of released DA from the synaptic extracellular space to facilitate its intraneuronal metabolism is achieved by a membrane transporter that controls the synaptic concentration. This transporter has been shown to be a 619 amino-acid protein with 12 hydrophobic membrane spanning domains (see Giros and Caron 1993). Although it has similar amino-acid sequences to that of the NA (and GABA) transporter, there are sufficient differences for it to show some specificity. Thus DA terminals will not concentrate NA and the DA transporter is blocked by a drug such as nomifensine which has less effect on NA uptake. Despite this selectivity some compounds, e.g. amphetamine and 6-OHDA (but not MPTP), can be taken up by both neurons. The role of blocking DA uptake in the central actions of cocaine and amphetamine is considered later (Chapter 23). 

R. Tyler-Cross and V. Schirch, Effects of amino acid sequence, buffers and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides, J. Biol. Chem, 266, 22549 (1991). 

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