Proteins, structure tertiary

S. Sun, Reduced representation approach to protein tertiary structure prediction statistical potential and simulated annealing, J. Theor. Biol. 172 (1995), 13-32. 

Protein tertiary structure is also influenced by the environment In water a globu lar protein usually adopts a shape that places its hydrophobic groups toward the interior with Its polar groups on the surface where they are solvated by water molecules About 65% of the mass of most cells is water and the proteins present m cells are said to be m their native state—the tertiary structure m which they express their biological activ ity When the tertiary structure of a protein is disrupted by adding substances that cause the protein chain to unfold the protein becomes denatured and loses most if not all of Its activity Evidence that supports the view that the tertiary structure is dictated by the primary structure includes experiments m which proteins are denatured and allowed to stand whereupon they are observed to spontaneously readopt their native state confer matron with full recovery of biological activity... 

N Srimvasan, TL Blundell. An evaluation of the performance of an automated procedure for comparative modelling of protein tertiary structure. Protein Eng 6 501-512, 1993. 

A Monge, R Friesner, B Elonig. An algorithm to generate low-resolution protein tertiary structures from knowledge of secondary structure. Proc Natl Acad Sci USA 91 5027-5029, 1994. 

Richardson, J.S. Describing patterns of protein tertiary structure. Methods Enzymol. 115 349-358, 1985. 

Simons KT, Kooperberg C, Huang E, Baker D. Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J Mol Biol 1997 268 209-25. 

In summary, formalin-treated does not significantly perturb the native structure of RNase A at room temperature. It also serves to stabilize the protein against the denaturing effects of heating as revealed by the increase in the denaturation temperature of the protein. However, formalin-treatment does not stabilize RNase A sufficiently to prevent the thermal denaturation of the protein at temperatures used in heat-induced AR methods as shown by both DSC and CD spectropolarimetry. This denaturation likely arrises from the heat-induced reversal of formaldehyde cross-links and adducts, as shown in Figure 15.4 of Section 15.4. Further, cooling formalin-treated RNase A that had been heated to 95°C for 10 min does not result in the restoration of the native structure of the protein, particularly in regard to protein tertiary structure. 

The engineering of zinc-binding sites in a-helical peptides, where metal binding stabilizes protein tertiary structure, has been reported by Handel and DeGrado (1990). In these experiments zinc-binding sites are incorporated into a dimeric helix-loop—helix peptide (H3 2) and a protein composed of four helices connected by three short loop sequences (H3 4). a model of one subunit of the H3 2 dimer is found in Fig. 47. In addition to metal complexation by two histidine residues at positions n and n+4 of one a helix, the metal is coordinated by a third histidine residue of an adjacent a helix. The composition of the zinc coordination polyhedron is like that of carbonic anhydrase (i.e., Hiss), and spectroscopic results suggest that all three histidine residues are involved in zinc complexation. This work sets an important foundation... 

In large proteins, tertiary structures can often be divided into domains. A domain is a region of a single peptide chain with a relatively compact structure it has folded... 

Many examples of recurring domain or motif structures are available, and these reveal that protein tertiary structure is more reliably conserved than primary sequence. The comparison of protein structures can thus provide much information about evolution. Proteins with significant primary sequence similarity, and/or with demonstrably similar structure and function, are said to be in the same protein family. A strong evolutionary relationship is usually evident within a protein family. For example, the globin family has many different proteins with both structural and sequence similarity to myoglobin (as seen in the proteins used as examples in Box 4-4 and again in the next chapter). Two or more families with little primary sequence similarity sometimes make use of the same major structural... 

Visualizing Folded Protein Structures Primary Structure Determines Tertiary Structure Secondary Valence Forces Are the Glue That Holds Polypeptide Chains Together Domains Are Functional Units of Tertiary Structure Predicting Protein Tertiary Structure Quaternary Structure Involves the Interaction of Two or More Proteins... 

We began the discussion of globular protein tertiary structure by pointing out that the secondary and tertiary structure is determined by the primary structure and that this is probably a reflection of the fact that the native folded conformation is the most stable structure that can be formed. If this is so, then it should be possible to predict a protein s structure from its primary sequence. At this juncture, such predictions remain an elusive goal. However, most proteins are made of a limited number of domains, which tend to reappear in many different proteins. Since this is the case, it may be possible to predict the structures of many proteins in the future by using the information accumulated from x-ray diffraction studies of related proteins. 

Structural domain. An element of protein tertiary structure that recurs in many structures. 

Pattison DI, Hawkins CL, Davies MJ (2007) Hypochlorous Acid-Mediated Protein Oxidation How Important Are Chloramine Transfer Reactions and Protein Tertiary Structure Biochemistry 46 9853... 

Disulfide bond exchange. Disulfide linkages are important in determining protein tertiary structure. Disulfide bond formation and/or exchange may occur during metal-catalyzed oxidation of the cysteine residue. This may lead to protein aggregation due to the formation of intermo-lecular disulfide bonds. In addition to cysteine disulfide bond formation, cysteine is susceptible to oxidation (Fig. 134) (200) (See also discussion on thiol chemistry earlier in this chapter). 

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