Factors determining secondary and tertiary structure

See also a-Helix, / -Sheet, Factors Determining Secondary and Tertiary Structure, Thermodynamics of Protein Folding, Dynamics of Protein Folding, Covalent Modifications to Regulate Enzyme Activity (from Chapter 11). 

See also Secondary Structure (General), Secondary Structure (Terms), Secondary Structures (Specific examples). Factors Determining Secondary and Tertiary Structure, Sheet, Keratin,... 

See also Globular Proteins, Factors Determining Secondary and Tertiary Structure, Thermodynamics of Protein Folding... 

The three-dimensional structure of a protein does not depend on environmental factors within the cell but is determined solely by the amino add sequence information (Epstein, 1963) this is called the Anfinsen dogma. Model systems of enzymes converted into linear polypeptide chains devoid of disulfide bonds and of secondary and tertiary structures support the theory that the folding process is essentially a thermodynamic one and that no genetic information other than that present in the amino acid sequence of the protein is required. 

A number of unexplained factors warrant mention. Orientation of elimination differs for secondary and tertiary structures. The peculiar predominance of cis- rather than /ra/ii-olefin may arise from the relative stabilities of the proton-olefin complexes. but a more certain conclusion would be possible if the stereochemistry of the dehydration in the acyclic series had been determined. Assumption of the anti stereospecificity known to be favoured by the cyclohexyl systems may be unsound especially in the light of the recent stereochemical findings in base-catalysed elimination reactions (Section 2..1.1(e)). The solution of the problem of the cis/trans ratios may lie in the duality of mechanism, namely the syn-clinallanti complexity. Certainly recent results on the dehydration of threo- and eo t/iro-2-methyl-4-deutero-3-pentanols on thoria show syn-clinal rather than anti stereospecificity as indicated by deuterium analysis of the cis- and /rn/iJ-4-methyl-2-pentenes, but in these cases the trans isomer was formed in a three-fold excess over the m-olefin . Of course, the dehydration reactions on the less acidic thoria may not be good models for alumina but a knowledge of stereochemistry in the acyclic series might prove an invaluable aid in the elucidation of the mechanism. There is obviously plenty of scope for future kinetic investigations which at the moment sadly lag behind preparative studies. 

In 1936 Mirsky and Pauling recognized the role of hydrogen bonds as important determinants of the secondary and tertiary structure of the proteins, in addition to intra-and interchain S—S linkages and ionic forces. More than a decade later hydrophobic interactions between certain amino acids were added as important conformational factors. That non-covalent linkages between proteins and non-protein compounds can determine the quaternary structure of a protein was shown in 1957 by the reconstitution of the tobacco mosaic virus from its isolated RNA and protein parts by Fraenkel-Conrat. On the other hand, Anfinsen< > could show that when the tertiary structure and activity of the bovine pancreas RNase are destroyed by reduction of its S—S linkages, re-oxidation of the SH groups finally leads to complete restitution of the enzymatic activity. Further structural studies of the reconstituted active enzyme support the assumption that in this case initial tertiary structure of the protein was restored. This supports the assumption that the tertiary structure of a protein is defined by its amino acid sequence. 

Keeping in mind all three DNA structure levels, primary, secondary, and tertiary, it is essential to understand that the lower level will mediate but not fully determine the higher structural level. In other words, the secondary as well as tertiary DNA structures of ODN in solution will be affected by many physical and chemical parameters, such as temperature, pH, salt content, compound concentration, etc. When evaluating complex biochemical systems, additional factors have to be taken into consideration possible interactions of ODN with a variety of other molecules and macromolecules in solution, local concentration effects and compartmentalization, biological half-life, etc. Hence when designing a DIMS ODN compound, its 3-D structure will not be fully predictable. 

Electrocatalytic investigations (185) on the preparation, properties, and long-term cathode performance of spongy Raney Ni type materials show that secondary structure (fine pores) and tertiary structure (coarser pores and cracks) depend on the chosen preparation procedure, and these factors determine the effective catalytic activity for the HER in a material way. Long-term performance is remarkably improved by controlled leaching of the Raney Ni alloy and oxidative aging (181,182,184) of the developed porous Raney Ni matrix. 

The macroscopic properties of liquid suspensions of fumed powders of silica, alumina etc. are not only affected by the size and structure of primary particles and aggregates, which are determined by the particle synthesis, but as well by the size and structure of agglomerates or mesoscopic clusters, which are determined by the particle-particle interactions, hence by a variety of product- and process-specific factors like the suspending medium, solutes, the solid concentration, or the employed mechanical stress. However, it is still unclear how these secondary and tertiary particle structures can be adequately characterized, and we are a long way from calculating product properties from them [1,2]. 

Details about ILs properties are covered in this book in the contributions by Seddon, Chiappe and Scott. However, two features deserve a comment for their possible consequences on reactivity and catalysis. First, depending on a delicate balance of entropie and enthalpic factors, including the polarity of the transition state structures with respect to regents, a reaction can be either speeded up or decelerated when carried out in an ionic liquid medium compared to a molecular solvent. An elegant study by Welton shows that in S-,2 reactions, primary, secondary and tertiary amines are more reactive as nucleophiles in ionic liquids, while halides react faster in conventional molecular solvents such as CH2CI2. In particular in a series of [Bmim] salts the order of nucleophilicity of halides is determined by the anion partner. To the same direction moves a kinetic study by Dyson on a cationic Ru(II) complex-catalysed hydrogenation of styrene in ILs, where it is clearly demonstrated that both the cation and the anion of the IL can inhibit or accelerate the formation of the active catalytic species. ... 

The other major factor determining the scope of the E2 reaction is the structure of the substrate. Primary, secondary and tertiary substrates can all react by the E2 mechanism (provided that there is a hydrogen atom on an adjacent carbon), although with primary and secondary substrates, the corresponding Sn2 reactions may compete effectively (tertiary substrates rarely react by the Sn2 mechanism). 

The influence of secondary structure on reactions of deamidation has been confirmed in a number of studies. Thus, deamidation was inversely proportional to the extent of a-helicity in model peptides [120], Similarly, a-hel-ices and /3-turns were found to stabilize asparagine residues against deamidation, whereas the effect of /3-sheets was unclear [114], The tertiary structure of proteins is also a major determinant of chemical stability, in particular against deamidation [121], on the basis of several factors such as the stabilization of elements of secondary structure and restrictions to local flexibility, as also discussed for the reactivity of aspartic acid residues (Sect. 6.3.3). Furthermore, deamidation is markedly decreased in regions of low polarity in the interior of proteins because the formation of cyclic imides (Fig. 6.29, Pathway e) is favored by deprotonation of the nucleophilic backbone N-atom, which is markedly reduced in solvents of low polarity [100][112],... 

The formation of stable secondary structures and a unique tertiary structure of proteins are dictated by the interactions between constituent amino acid residues along the polypeptide chain and by their interactions with the surrounding medium. During the process of protein folding, the hydrophobic force drives the polypeptide chain to the folded state and overcomes the entropic factors while hydrogen bonds, ion pairs, disulhde bonds, and van der Waals interactions define the shape and keep it from falling apart. The structure of a protein mainly dictates its function, and the attainment of stable conformation is essential for proper function. Hence, many methods have been developed to determine the three-dimensional structures of proteins experimentally. 

As the chain length increases further, other factors come into play to determine the overall conformation of the peptide and the electrically charged groups at the ends of the chain are less important in this respect. Interactions, repulsive and attractive, between side-chains are dominant and the primary structure (the sequence of the peptide and the stereochemistry at each chiral centre) determines the run of the peptide chain through the molecule (the secondary structure) and the overall shape of a single polypeptide chain (globular, extended, etc. the tertiary structure) of the molecule. 

---