Chemical protein function

Chemical and Functional Properties of Food Proteins Edited by Zdzislaw E. Sikorski... 

O Hare, H. M., Johnsson, K. and Gautier, A. (2007). Chemical probes shed light on protein function. Curr. Opin. Struct. Biol. 17, 488-94. 

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. 

To date, the lipids so far used have been mainly extracts from natural sources such as EPC and archaeal lipids[17,18] The chemical stability of EPC, however, is not sufficient and the membrane permeability to H1 is sometimes too high for quantitative analyses of membrane protein functions. Though archaeal lipids display many preferable features for... 

Fig. 3.14 Schematic representation of noncovalent interaction (/.e., n-stacking) between the CNT surface and a pyrene derivative for protein functionalization. Adapted with permission from [74], 2009, American Chemical Society.

Several laboratories have replaced consecutive amino acids with cysteine residues as part of a technique called the substituted cysteine accessibility method (SCAM) (Akabas et al., 1992). In this technique, which is described elsewhere in this volume, the accessibihty of the inserted cysteine residues to an aqueous environment is measured by their accessibihty to covalent chemical modifying agents. The effects of the addition of these bulky agents can then be used to explore protein functional domains such as those that line ion channels or ligand binding sites. 

Sikorski, Z.E. (2002). Chemical reactions of proteins in food systems, in Sikorski, Z.E., ed.. Chemical and Functional Properties of Food Proteins, CRC Press, Boca Raton, 191-216. 

Advances in chemical synthesis have enabled considerable sophistication in the construction of diverse compound libraries to probe protein function [61, 62). However, few general techniques exist that can directly assess binding mechanisms and evaluate ligand afEnities in a multiplexed format. To realize the full potential of combinatorial chemistry in the drug discovery process, generic and efficient tools must be applied that combine mixture-based techniques to characterize protein-ligand interactions with the strengths of diversity-oriented chemical synthesis. 

We need to have drugs, antidotes, and cures for the weapons of mass destruction that terrorists are likely to use. To develop medicinal countermeasures, the basic science involved must first be understood. For both chemical and biological weapons, the process of molecular recognition by elements of the human body is of utmost importance. However, we do not have a clear understanding of protein surface interactions, the relationship of genes to protein function, and how viruses infect and replicate. All of these processes are chemical in nature and caimot be solved without knowledge of the chemical sciences. 

The importance of single-bond conformation is nevermore apparent than for polypeptides. Here, distinct local domains involving a-helices and P-sheets (among other structures) occur commonly, and these in turn dictate overall (tertiary) stmcture of proteins and ultimately protein function. Interestingly, proteins appear to exhibit well-defined shapes, that is, exist as a single conformer or a very few closely-related conformers. This is the reason that they can be crystallized and their structures determined, and is certainly a major factor behind the ability of proteins to direct specific chemical reactions. 

To date, complex proteins with biological activity (6), for use in X-ray crystal structure analysis (7) and ELISA systems (8), and for the development of animal drugs (9) have successfully been produced by using this system. Therefore, the Kaiko-baculovirus protein production system has broad applicability across the field of reverse chemical genetics for the analysis of protein function on the basis of interactions with chemical compounds. 

Phosphorylation on serine, threonine, and tyrosine residues is an extremely important modulator of protein function. Phosphorylation can be analyzed by mass spectrometry with enrichment of compounds of interest using immobilized metal affinity chromatography and chemical tagging techniques, detection of phosphopep-tides using mass mapping and precursor ion scans, localization of phosphorylation sites by peptide sequencing, and quantitation of phosphorylation by the introduction of mass tags (McLachlin and Chait 2001). 

High molecular weight and random coil structure of protein result in more associations and thereby enhance adhesive and cohesive properties. Although these characteristics are inherent in native gluten proteins, functional properties of other proteins may be improved by chemical or thermal processing. 

It is essential to consider the physico-chemical properties of each WPC and casein product in order to effectively evaluate their emulsification properties. Otherwise, results merely indicate the previous processing conditions rather than the inherent functional properties for these various products. Those processing treatments that promote protein denaturatlon, protein-protein Interaction via disulfide interchange, enzymatic modification and other basic alterations in the physico-chemical properties of the proteins will often result in protein products with unsatisfactory emulsification properties, since they would lack the ability to unfold at the emulsion interface and thus would be unable to function. It is recommended that those factors normally considered for production of protein products to be used in foam formation and foam stabilization be considered also, since both phenomena possess similar physico-chemical and functionality requirements (30,31). 

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