2 Структура и функция белка (1160071), страница 17
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Optimizing the hydrogen bonding of water around a hydrophobic molecule results in theformation of a highly structured shell or solvation layer of water in theimmediate vicinity, resulting in an unfavorable decrease in the entropy of water. The association among hydrophobic or nonpolar groupsresults in a decrease in this structured solvation layer, or a favorableincrease in entropy. As described in Chapter 4, this entropy term is themajor thermodynamic driving force for the association of hydrophobicgroups in aqueous solution, and hydrophobic amino acid side chainstherefore tend to be clustered in a protein's interior, away from water.The formation of hydrogen bonds and ionic interactions in a protein is also driven largely by this same entropic effect.
Polar groups cangenerally form hydrogen bonds with water and hence are soluble inwater. However, the number of hydrogen bonds per unit mass is generally greater for pure water than for any other liquid or solution, andthere are limits to the solubility of even the most polar molecules because of the net decrease in hydrogen bonding that occurs when theyare present. Therefore, a solvation shell of structured water will alsoform to some extent around polar molecules. Even though the energy offormation of an intramolecular hydrogen bond or ionic interaction between two polar groups in a macromolecule is largely canceled out bythe elimination of such interactions between the same groups andwater, the release of structured water when the intramolecular interaction is formed provides an entropic driving force for folding.
Most ofthe net change in free energy that occurs when weak interactions areformed within a protein is therefore derived from the increase in entropy in the surrounding aqueous solution.Of the different types of weak interactions, hydrophobic interactions are particularly important in stabilizing a protein conformation;the interior of a protein is generally a densely packed core of hydrophobic amino acid side chains.
It is also important that any polar orcharged groups in the protein interior have suitable partners for hydrogen bonding or ionic interactions. One hydrogen bond makes only asmall apparent contribution to the stability of a native structure, butthe presence of a single hydrogen-bonding group without a partner inthe hydrophobic core of a protein can be so destabilizing that conformations containing such a group are often thermodynamically untenable.Most of the structural patterns outlined in this chapter reflectthese two simple rules: (1) hydrophobic residues must be buried in theprotein interior and away from water, and (2) the number of hydrogenbonds must be maximized.
Insoluble proteins and proteins withinmembranes (Chapter 10) follow somewhat different rules because oftheir function or their environment, but weak interactions are stillcritical structural elements.Protein Secondary StructureSeveral types of secondary structure are particularly stable and occurwidely in proteins. The most prominent are the a helix and (3 conformations described below. Using fundamental chemical principles and afew experimental observations, Linus Pauling and Robert Corey predicted the existence of these secondary structures in 1951, severalyears before the first complete protein structure was elucidated.Linus PaulingRobert Corey1897-1971Part II Structure and CatalysisIn considering secondary structure, it is useful to classify proteinsinto two major groups: fibrous proteins, having polypeptide chains arranged in long strands or sheets, and globular proteins, with polypeptide chains folded into a spherical or globular shape.
Fibrous proteinsplay important structural roles in the anatomy and physiology of vertebrates, providing external protection, support, shape, and form. Theymay constitute one-half or more of the total body protein in largeranimals. Most enzymes and peptide hormones are globular proteins.Globular proteins tend to be structurally complex, often containingseveral types of secondary structure; fibrous proteins usually consistlargely of a single type of secondary structure. Because of this structural simplicity, certain fibrous proteins played a key role in the development of the modern understanding of protein structure and provideparticularly clear examples of the relationship between structure andfunction; they are considered in some detail after the general discussion of secondary structure.The Peptide Bond Is Rigid and PlanarPauling and Corey began their work on protein structure in the late1930s by first focusing on the structure of the peptide bond.
The acarbons of adjacent amino acids are separated by three covalent bonds,arranged Ca—C—N—Ca. X-ray diffraction studies of crystals of aminoacids and of simple dipeptides and tripeptides demonstrated that theamide C—N bond in a peptide is somewhat shorter than the C—Nbond in a simple amine and that the atoms associated with the bondare coplanar. This indicated a resonance or partial sharing of two pairsof electrons between the carbonyl oxygen and the amide nitrogen (Fig.0~I^NHH(a)Qto.124nm0.153nm\\0.1460.132\AminoterminusCarboxylterminusnm(c)Figure 7—4 (a) The planar peptide group. Eachpeptide bond has some double-bond character dueto resonance and cannot rotate. The carbonyl oxygen has a partial negative charge and the amidenitrogen a partial positive charge, setting up asmall electric dipole.
Note that the oxygen and hydrogen atoms in the plane are on opposite sides ofthe C—N bond. This is the trans configuration. Virtually all peptide bonds in proteins occur in thisconfiguration, although an exception is noted inFig. 7-10. (b) Three bonds separate sequential Cacarbons in a polypeptide chain. The N—Ca andCa—C bonds can rotate, with bond angles designated 4> and ip, respectively, (c) Limited rotationcan occur around two of the three types of bonds ina polypeptide chain.
The C—N bonds in the planarpeptide groups (shaded in blue), which make upone-third of all the backbone bonds, are not free toChapter 7 The Three-Dimensional Structure of Proteins7-4a). The oxygen has a partial negative charge and the nitrogen apartial positive charge, setting up a small electric dipole. The fouratoms of the peptide group lie in a single plane, in such a way that theoxygen atom of the carbonyl group and the hydrogen atom of the amidenitrogen are trans to each other. From these studies Pauling and Coreyconcluded that the amide C—N bonds are unable to rotate freely because of their partial double-bond character.
The backbone of a polypeptide chain can thus be pictured as a series of rigid planes separatedby substituted methylene groups, —CH(R)— (Fig. 7-4c). The rigidpeptide bonds limit the number of conformations that can be assumedby a polypeptide chain.Rotation is permitted about the N—Ca and the Ca—C bonds. Byconvention the bond angles resulting from rotations are labeled <>/ (phi)for the N—Ca bond and <>/ (psi) for the Ctt—C bond. Again by convention, both (f> and ip are defined as 0° in the conformation in which thetwo peptide bonds connected to a single a carbon are in the same plane,as shown in Figure 7-4d.
In principle, 4> and I)J can have any valuebetween -180° and +180°, but many values of <>/ and \\t are prohibitedby steric interference between atoms in the polypeptide backbone andamino acid side chains. The conformation in which cj) and I/J are both 0°is prohibited for this reason; this is used merely as a reference point fordescribing the angles of rotation.Every possible secondary structure is described completely by thetwo bond angles <f> and i// that are repeated at each residue. Allowedvalues for <>/ and i/> can be shown graphically by simply plotting \pversus </>, an arrangement known as a Ramachandran plot.
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