Inhibitors primary structure

The CXC chemokines can be divided into two groups on the basis of a structure/function domain consisting of the presence or absence of three amino acid residues (Glu-Leu-Arg ELR motif) that precedes the first cysteine amino acid residue in the primary structure of these cytokines. The ELR+ CXC chemokines are chemoattractants for neutrophils and act as potent angiogenic factors (6). In contrast, the ELR" CXC chemokines are chemoattractants for mononuclear cells and are potent inhibitors of angiogenesis (Table 1) (6). 

Cholinesterases secreted by parasitic nematodes of (predominantly) the alimentary tract or other mucosal tissues are authentic AChEs when analysed by substrate specificity, inhibitor sensitivities and primary structure. In the first two respects, they resemble vertebrate AChEs, whereas somatic (and therefore presumably neuronal) enzymes of nematodes analysed to... 

MAO A and B differ in primary structure and in substrate specificity [5,7]. The two isozymes, located on the mitochondrial outer membranes, have 70% homology in peptide sequence and share common mechanistic details. It is now recognized that these are different proteins encoded by different genes, but probably derived from a common ancestral gene. Crystal structures for both MAO A and B complexes with inhibitors have recently been reported [8]. Serotonin is selectively oxidized by MAO A, whereas benzylamine and 2-phenylethylamine are selective substrates for MAO B. Dopamine, norepinephrine, epinephrine, trypt-amine, and tyramine are oxidized by both MAO A and B in most species [9]. In addition, MAO A is more sensitive to inhibition by clorgyline (1), whereas MAO B is inhibited by low concentrations of L-deprenyl ((f )-( )-deprenyl) (2) [5,6cj. Development of inhibitors that are selective for each isozyme has been an extremely active area of medicinal chemistry [8]. 

In studies with a sulfonyl-resistant biotype of redroot pigweed, the first weed in Israel to exhibit ALS resistance, Sibony et al. (2001) found it was cross-resistant to all other classes of ALS herbicides. From nucleotide sequencing, they concluded that a proline to leucine change in Domain A at position 248 is the only difference in the amino acid primary structure of the regions sequenced, indicating that it is responsible for all ALS inhibitor resistance observed. 

Twelve ACE-inhibitory peptides have been identified from sardine muscle hydrolysate, revealing that a dipeptide, Val-Tyr, acts as a key inhibitor (Matsufuji et al., 1994). Of the identified ACE-inhibitory peptides, the tripeptides (Leu-Arg-Pro, lie-Val-Tyr) and the dipeptide (Val-Tyr) show strong inhibitory activity. Moreover, two inhibitory peptides (myopentapep-tides A and B) have been purified from a thermolysin digest of porcine skeletal muscle proteins. The sequences were found in the primary structure of the myosin heavy chain (Arihara et al., 2001). 

Prior to the start of any experimental substrate finding activity, databases should be mined. A tremendous amount of information about proteases, substrates, inhibitors, and structures can be retrieved from two searchable databases MEROPS (Rawlings et al., 2006) (http //merops.sanger. ac.uk) and BRENDA (www.brenda-enzymes.de), that serve as good starting points for assay development in many cases. These databases are available to the public and should be consulted as primary sources of information. 

S. Murao, K.Tanaka, and I. Nojima, Primary structure of paim I, an alpha-amylase inhibitor from Streptomyces corchorushii, determined by the combination of Edman degradation and fast atom bombardment mass spectrometry, Biochemistry 26 (1987), 6483-6488. 

In both bacteria and eucarya the susceptibility to certain ribosome-targeted inhibitors correlates with specific primary structural features of rR24A, or with features of the ribosomal domain that acts as the antibiotic binding sites. Firstly, resistance to specific ribosome-directed drugs is conferred by single-base changes within phylogenetically... 

Carmichael, D. R, Sommer, A., Thompson, R. C. et al. (1986). Primary structure and cDNA cloning of human fibroblast collagenase inhibitor. Proc. Natl. Acad. Sci. USA 85, 2407-2411. 

Fig. 5.6. Secondary structure of the /3 subunit of E. coli F,. The primary structure of the protein was deduced from the DNA sequence [11]. The binding residues and numbers of binding sites for covalent inhibitors are also shown.

K. Hatano, M. Kojima, M. Tanokura, and K. Takahashi. Primary structure, sequence-specific H-NMR assignments and secondary structure in solution of bromelain inhibitor VI from pineapple stem. Eur. J. Biochem. 232 335 (1995). 

Intracellular biodegradation of CGP is mediated by cyanophycinase (CphB) (reviewed by [116]). Products of the degradation mechanism are usually [3-dipeptides which are then split to free amino acids by intracellular dipeptidases. CphB shows a high specificity for CGP as a substrate and is inhibited by serine protease inhibitors. Its primary structure reveals a serine residue within a lipase box motif (Gly-Xaa-Ser-Xaa-Gly) which forms a catalytic triad together with a glutamic acid and a histidine residue. 

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