Proteins conformational stability

Eyles, S.J., Speir, J. P., Kruppa, G.H., Gierasch, L. M., and Kaltashov, I.A. (2000) Protein conformational stability probed by Fourier transform ion cyclotron resonance mass spectrometry, J. Am. Chem. Soc. 122, 495-500. 

Quinn EA, Forbes RT, Williams AC, Oliver MJ, McKenzie L, and Purewas TS. Protein Conformational Stability in the Hydroxyfluoroalkane Propellants Tetrafluoroethane and Heptafluoropropane Analyzed by Fourier Transform Raman Spectroscopy. IntJPharm 1999 186 31-41. 

Shirley B A (1992). Protein conformational stability estimated from urea, guanidine hydrochloride, and thermal denaturation curves. In T J Ahern, M C Manning, (eds.). Stability of Protein Pharmaceuticals Part A Chemical and Physical Pathways of Protein Degradation Plenum Press, New York, pp. 167-194. 

Schwehm, J. M., and Stites, W. E. (1998). Application of automated methods for determination of protein conformational stability. Methods Enzymol. 295, 150-170. 

Protein conformational stability Is not only of fundamental Interest for protein chemistry, but also relevant to questions of food safety and quality. High stability of proteinase Inhibitors may necessitate use of conditions for their Inactivation that denature other proteins first and lead to other reactions that have undesirable consequences for protein digestibility (Richardson, 1977). In discussing Inactivation of enzymes during food processing. Balls (1942) stated, "Until we know more about It, we shall probably overheat our products rather than underheat them, just to be safe. When we know more about It we may be able to moderate our enthusiasm and our technique". Basic studies on stabilities of protein enzyme Inhibitors and lectins, as well as enzymes, can contribute to development of methods that avoid overheating or underheating food or feed products. 

Creighton, T. E. (1983). An empirical approach to protein conformational stability and flexibility. Biopolymers 22, 49-58. 

C. N. Protein conformational stabilities can be determined from hydrogen exchange rates. Nat. Struct. Biol. 1999, 6(10), 910-912. 

An understanding of a wide variety of phenomena concerning conformational stabilities and molecule-molecule association (protein-protein, protein-ligand, and protein-nucleic acid) requires consideration of solvation effects. In particular, a quantitative assessment of the relative contribution of hydrophobic and electrostatic interactions in macromolecular recognition is a problem of central importance in biology. 

Several different kinds of noncovalent interactions are of vital importance in protein structure. Hydrogen bonds, hydrophobic interactions, electrostatic bonds, and van der Waals forces are all noncovalent in nature, yet are extremely important influences on protein conformations. The stabilization free energies afforded by each of these interactions may be highly dependent on the local environment within the protein, but certain generalizations can still be made. 

The factors accounting for the stabilization of protein conformation are shown in... 

While loops lack apparent stmcmral regularity, they exist in a specific conformation stabilized through hydrogen bonding, salt bridges, and hydrophobic interactions with other portions of the protein. However, not all portions of proteins are necessarily ordered. Proteins may contain disordered regions, often at the extreme amino or carboxyl terminal, characterized by high conformational flexibility. In many instances, these disor-... 

Protein conformation is also markedly affected by the concentration and type of ionic species present. In solution, individual salt effects can be either stabilizing or denaturing [26,27], These effects correspond to the Hofmeister lyotropic series ... 

Molecular insight into the protein conformation states of Src kinase has been revealed in a series of x-ray crystal structures of the Src SH3-SH2-kinase domain that depict Src in its inactive conformation [7]. This form maintains a closed structure, in which the tyrosine-phosphorylated (Tyr527) C-terminal tail is bound to the SH2 domain (Fig. 2). The x-ray data also reveal binding of the SH3 domain to the SH2-kinase linker [adopts a polyproline type II (PP II) helical conformation], providing additional intramolecular interactions to stabilize the inactive conformation. Collectively, these interactions cause structural changes within the catalytic domain of the protein to compromise access of substrates to the catalytic site and its associated activity. Significantly, these x-ray structures provided the first direct evidence that the SH2 domain plays a key role in the self-regulation of Src. 

The R groups of the non-polar, alipathic amino acids (Gly, Ala, Val, Leu, lie and Pro) are devoid of chemically reactive functional groups. These R groups are noteworthy in that, when present in a polypeptide s backbone, they tend to interact with each other non-covalently (via hydrophobic interactions). These interactions have a significant stabilizing influence on protein conformation. 

In summary, the formation of silk fibers involves superstructures such as, possibly, micelles and/or molecular rods (Akai, 1998 Jin and Kaplan, 2003 Knight and Vollrath, 2002) that are dependent on the packing and conformation of the individual protein units. The relationship, however, between the shapes of these superstructures and the various forms of protein conformation remains elusive (Valluzzi and Jin, 2004). Seeking to clarify this issue we will examine, in Section II.B, the role of shape and extended network formation modulating solubility, stability, and assembly. 

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