Serine properties

As these experiments with engineered mutants of trypsin prove, we still have far too little knowledge of the functional effects of single point mutations to be able to make accurate and comprehensive predictions of the properties of a point-mutant enzyme, even in the case of such well-characterized enzymes as the serine proteinases. Predictions of the properties of mutations using computer modeling are not infallible. Once produced, the mutant enzymes often exhibit properties that are entirely surprising, but they may be correspondingly informative. 

Subtilisins are a group of serine proteinases that are produced by different species of bacilli. These enzymes are of considerable commercial interest because they are added to the detergents in washing powder to facilitate removal of proteinaceous stains. Numerous attempts have therefore recently been made to change by protein engineering such properties of the subtilisin molecule as its thermal stability, pH optimum, and specificity. In fact, in 1988 subtilisin mutants were the subject of the first US patent granted for an engineered protein. 

Table 1 presents the chemical composition and some properties of both gums reported by Osman et al., 1993 and Williams Phillips, et al., 2000. Despite having different protein content, amino acid composition is similar in both gums. Recently, Mahendran et al., 2008, reported the GA amino acid composition in Acacia Senegal, being rich in hydroxyproline, serine, threonine, leucine, glycine, histidine. Table 2. 

Early mutational studies of the Rieske protein from 6ci complexes have been performed with the intention of identifying the ligands of the Rieske cluster. These studies have shown that the four conserved cysteine residues as well as the two conserved histidine residues are essential for the insertion of the [2Fe-2S] cluster (44, 45). Small amounts of a Rieske cluster with altered properties were obtained in Rhodobacter capsulatus when the second cysteine in the cluster binding loop II (Cys 155, corresponding to Cys 160 in the bovine ISF) was replaced by serine (45). The fact that all four cysteine residues are essential in Rieske clusters from be complexes, but that only two cysteines are conserved in Rieske-type clusters, led to the suggestion that the Rieske protein may contain a disulfide bridge the disulfide bridge was finally shown to exist in the X-ray structure (9). 

The primary structure of a polypeptide is its sequence of amino acids. It is customary to write primary structures of polypeptides using the three-letter abbreviation for each amino acid. By convention, the structure is written so that the amino acid on the left bears the terminal amino group of the polypeptide and the amino acid on the right bears the terminal carboxyl group. Figure 13-35 shows the two dipeptides that can be made from glycine and serine. Although they contain the same amino acids, they are different molecules whose chemical and physical properties differ. Example shows how to draw the primary stmcture of a peptide. 

DPP-4 is a serine protease that inactivates GLP-1. GLP-1 stimulates insulin secretion and suppresses glucagon release. The inhibition of DPP-4 prolongs the half-life of GLP-1 and brings about beneficial effects on glucose levels and glucose tolerance in type 2 diabetics. Backes et al. [64] report on the parallel optimization of enzyme binding affinity and inhibition, selectivity, ADME properties, and PK (Scheme 19). 

The physical properties of the synthetic glycosyl derivatives of l-asparagine, L-serine, and L-threonine are reported in Tables I-V. Derivatives characterized otherwise, but without m.p. and optical rotation, have also been included. Whenever more than one reference is given, the physical constants are taken from the references printed in bold letters. The abbreviations used in the m.p. column are as follows foam., foaming dec., decomposing and soft., softening. 

Konarev AV, Anisimova IN, Gavrilova VA, et al. Serine proteinase inhibitors in the Compositae distribution, polymorphism and properties. Phytochemistry 2002 59 279-291. 

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