Sequence conformational stability

Another example of a quantal repeat—but with considerable variation in sequence—is seen in the keratin-associated proteins (KAPs). In sheep, these display pentapeptide and decapeptide consensus repeats of the form G—G—Q—P—S/T and C-C-Q/R—P—S/T—C/S/T—C—Q—P/T—S, respectively (Parry et al., 1979). Some of the positions, as indicated by the presence of a consensus sequence, contain residues that occur much more frequently than others, but the absolute conservation of a residue in any position is not observed. The decapeptide consists of a pair of five-residue repeats closely related, but different to that displayed by the pentapeptide. Although the repeats have an undetermined structure, the similarity of the repeat to a sequence in snake neurotoxin suggests that the pentapeptides will adopt a closed loop conformation stabilized by a disulphide bond between cysteine residues four apart (Fig. 5 Fraser et al., 1988 Parry et al, 1979). Relative freedom of rotation about the single bond connecting disulphide-bonded knots would give rise to the concept of a linear array of knots that can fold up to form a variety of tertiary structures. The KAPS display imperfect disulphide stabilization of knots and have interacting... 

Deprez, P., Doss-Pepe, E., Brodsky, B., and Inestrosa, N. C. (2000). Interaction of the collagen-like tail of asymmetric acetylcholinesterase with heparin depends on triple-helical conformation, sequence and stability. Biochem. J. 350, 283-290. 

Primary, secondary, tertiary, and quaternary structure are familiar concepts for proteins and refer to the amino acid sequence, local folding arrangement, three-dimensional organization, and subunit interactions of polypeptide chains, respectively. Here, tertiary and quaternary structure shall be considered in the most general way, to include also the small molecules or ions that are essential for the conformational stability of the polypeptide chains. This is especially relevant for halophilic proteins, which have extensive interactions with solvent components (water molecules and salt ions). The known structure of a protein (at any level) always results from experiment, and as such is known only within appropriate error limits. 

Casadio, R., Compiani, M Fariselli, P. Vivarelli, F. (1995). Predicting free energy contributions to the conformational stability of folded proteins from the residue sequence with radial basis function networks. Intelligent Systems for Molecular Biology 3,81-8. 

The composition of proteins is variable. The percentage of a certain amino acid may readily vary by a factor of 10 among a number of proteins. Some amino acids do not occur in some proteins, notably Cys. The composition largely determines the nutritional quality and to a considerable extent the chemical reactivity of a protein. Most other properties depend on the primary structure, i.e., the sequence of amino acid residues, because the primary structure determines the higher structures (see below), which in turn determine properties like conformational stability and solubility. Never-... 

Boxmd, P. D., et ah, Streptokinase triggers conformational activation of plasminogen through specific interactions of the amino-terminal sequence and stabilizes the active zymogen conformation. / Biol Chem 2001, 276, 26084-26089. 

The linear sequence of nucleotides linked by phosphodiester bonds constitutes the primary structure of nucleic acids. Like polypeptides, polynucleotides can twist and fold Into three-dimensional conformations stabilized by noncovalent bonds. Although the primary structures of DNA and RNA are generally similar, their three-dimensional conformations are quite different. These structural differences are critical to the different functions of the two types of nucleic acids. 

Replacement of two or more of the OH groups with other groups such as H, Me, SH, and NH2 similarly affects the order of conformational stability. For example, molecular mechanics calculations using the MM3 program predict the stability sequences for the tetradeoxy compound 95e tp be cone > partial cone > 1,3-alternate > 1,2-alternate and that of the tetramethyl compound 95k to be 1,3-alternate partial cone > 1,2-alternate > 1,3-alternate. 

Fluorinated amino acids have been incorporated into the hydrophobic cores of coiled coils in order to modulate physical and biological properties of the ensembles and quantify resulting changes in conformational stability. Coiled-coil motifs, wherein two or more helical peptide strands interact to form higher order structures, are ubiquitous in nature and have been well studied. They contain a typical heptad repeat sequence (abcdefg) in which positions a and d make up the hydrophobic core and charged residues at positions e and g interact electrostatically. Amino acids in coiled-coil... 

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