Proteins elucidation

Amino acids, peptides and proteins play essential roles in living systems. As chemists, we have the ability to fabricate new structures of great complexity. Yet frequently the synthesis and application of even the simplest chemical structures can contribute substantial information on living systems. This has certainly been true for the application of fluorine chemistry to the synthesis of fluorinated amino acids [1, 2], These molecules are not only interesting in their own right but may act as potent mechanism-based enzyme inhibitors that may have application in medicine or diagnostics, or they can be valuable probes that, incorporated into peptides or proteins, elucidate fundamental biological chemistry or uncover new aspects of biochemical structure and function [3-5],... 

Proteins for pharmaceutical use should not have modified side chains. The common method for detection of modified residues is to see a blank space instead of a peak in the HPLC elution trace of the amino acid analysis or a band at another position than the amino acid indicated by the gene sequence. This analysis will probably not detect modifications that affect only a small fraction of the protein. Elucidation of the identity of the modified side chains, if one can locate them, requires some astute chemistry. For example, in phycocyanine, N-methyl-asparagine ran exactly at the position of serine Identification of the modified residue relied on detection of methyl amine released by acid hydrolysis of the protein. ... 

Degradation of Polypeptides and Proteins. Elucidation of Organic Structures... 

Having settled on a definition of chemoinformatics, it is time for us to reflect on the distinction between chemoinformatics and bioinformatics. The objects of interest of bioinformatics are mainly genes and proteins. But genes, DNA and RNA, and proteins are chemical compounds They are objects of high interest in chemistry, Chemists have made substantial contributions to the elucidation of the structure and function of nucleic adds and proteins. The message is dear there is no clearcut distinction between bioinfonnatics and chemoinformatics I... 

Several human receptors for the neurohypophyseal hormones have been cloned and the sequences elucidated. The human V2 receptor for antidiuretic hormone presumably contains 371 amino acids and seven transmembrane segments and activates cycHc AMP (76). The oxytocin receptor is a classic G-protein-coupled type of receptor with a proposed membrane topography also involving seven transmembrane components (84). A schematic representation of the oxytocin receptor stmcture within the membrane is shown in Eigure 4 (85). 

In 1974, a petition for affiimation of the GRAS status of miracle fmit was submitted by the Miralin Company, mainly based on the fact that miracle fmits have been consumed by humans since before 1958. In 1977, the petition was denied by the FDA. However, miraculin remains a research curiosity. Its stmcture was elucidated in 1989 (125). Another protein, curculin [151404-13-6] (126), has also been reported to exert a sweet-inducing activity similar to miraculin. 

Replacement of the sulfur atom in the thiosemicarba2one moiety by an oxygen atom leads to a loss of antiviral activity. Methisa2one has no significant effect on vaccinia vims DNA synthesis (14) but seems to inhibit late protein synthesis by a mechanism that remains to be elucidated. 

As the molecular structure of DNA was being elucidated, scientists made significant contributions to revealing the structures of proteins and enzymes. Sanger [2] resolved the... 

The subtilisin mutants described here illustrate the power of protein engineering as a tool to allow us to identify the specific roles of side chains in the catalytic mechanisms of enzymes. In Chapter 17 we shall discuss the utility of protein engineering in other contexts, such as design of novel proteins and the elucidation of the energetics of ligand binding to proteins. 

In this chapter we describe some examples of structures of membrane-bound proteins known to high resolution, and outline how the elucidation of these structures has contributed to understanding the specific function of these proteins, as well as some general principles for the construction of membrane-bound proteins. In Chapter 13 we describe some examples of the domain organization of receptor families and their associated proteins involved in signal transduction through the membrane. 

Despite considerable efforts very few membrane proteins have yielded crystals that diffract x-rays to high resolution. In fact, only about a dozen such proteins are currently known, among which are porins (which are outer membrane proteins from bacteria), the enzymes cytochrome c oxidase and prostaglandin synthase, and the light-harvesting complexes and photosynthetic reaction centers involved in photosynthesis. In contrast, many other membrane proteins have yielded small crystals that diffract poorly, or not at all, using conventional x-ray sources. However, using the most advanced synchrotron sources (see Chapter 18) it is now possible to determine x-ray structures from protein crystals as small as 20 pm wide which will permit more membrane protein structures to be elucidated. 

In one of the early experiments designed to elucidate the genetic code, Marshall Nirenberg of the U.S. National Institutes of Health (Nobel Prize in physiology or medicine, 1968) prepared a synthetic mRNA in which all the bases were uracil. He added this poly(U) to a cell-free system containing all the necessary materials for protein biosynthesis. A polymer of a single amino acid was obtained. What amino acid was polymerized ... 

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