Serine proteases trypsin

Acylation reaction, 171 Alanine, structure of, 110 Alcohol dehydrogenase, 205 Amide hydrolysis, see also Serine proteases Trypsin... 

For instance, the mammalian serine proteases — trypsin, chymotrypsin, and elastase—are very similar in structure and conformation. If a new mammalian serine protease is discovered, and sequence homology with known proteases... 

Pancreatic fluid, secreted in the duodenum is composed of digestive enzymes and bicarbonate. The two major pancreatic proteases are the serine proteases trypsin and chymotrypsin. 

The substrate specificity of an enzyme is determined by the properties and spatial arrangement of the amino acid residues forming the active site. The serine proteases trypsin, chymotrypsin and elastase cleave peptide bonds in protein substrates on the carboxyl side of positively charged, aromatic and small side-chain amino acid residues, respectively, due to complementary residues in their active sites. 

We have created efficient syntheses of remarkably potent and selective bifunctional tryptase inhibitors, which are also competitive and reversible, containing pyran moieties and hetero and non-hetero aryl diynes as scaffolds. Several modifications at the core templates and the linker moieties are well tolerated without significant loss of inhibition activity. In contrast with previous results published recently [32], it was also apparent from the aryl diyne inhibitors that the distance between the two terminal amino groups can be considerably less than 30 bonds in highly potent target compounds (e.g. 9 and 29 with 26 bonds each). The in-vitro potencies of the compounds were between 1 im for 26 and 1.3 nM for 15 with high selectivity against other serine proteases (trypsin, thrombin, and factor Xa, respectively) in... 

The cereal dual function a-amylase/trypsin inhibitor proteins are cysteine-rich, disulphide-rich, double-headed, 13-16 kDa, dual function inhibitor proteins that inhibit both of the digestion enzymes a-amylase and trypsin [290-325] (Table 11). Thus the Zea (com) member of this family, com Hageman factor inhibitor (CHFI), is a double-headed 14 kDa protein that inhibits a-amylase and the serine proteases trypsin and blood clotting Factor Xlla [323-324] (Table 11). The structures of the bifunctional a-amylase/trypsin inhibitor proteins from Eleusine (ragi) (RBI) [292-295] and Zea (com) (CHFI) [325] have been determined. These proteins are structurally similar to the lipid transfer proteins, being composed of a bundle of 4 a-helices together with a short [3-sheet element connected by loops, the a-amylase- and protease-inhibitory domains being separately located [325]. 

Serine protease (trypsin family) released during inflammation... 

Thrombin is a proteolytic enzyme and has a remarkable similarity in its overall three-dimensional structure to the digestive serine proteases, trypsin, and chymotrypsin [11-13]. Trypsin and thrombin share a common primary specificity for proteolysis next to arginine or lysine residues. Structural data of thrombin and trypsin have demonstrated strong resemblance in their substrate sites, and many small organic inhibitors are comparably active against both the enzymes [14,15]. For this reason, no or low inhibition of trypsin is viewed as a required condition for a compoimd to be a successful orally bioavailable thrombin inhibitor [16]. 

FIGURE 1. (A) Catalytic triad in the serine protease trypsin (PDB ID lAKS), wherein the nucle-ophilicity of the nucleophilic Serl95 is dramatically enhanced by H-bonding (dotted lines) with H57. (B) The metaUotriad active site in serralysin (PDB ID ISRP), showing the sandwiched nucleophihc water (in the form of hydroxide) by the active-site Zn(II) and Glul77 via a coordination bond and a H-bond... 

For example, enzyme degradation of insulin is known to be mediated by the serine proteases trypsin, a-chymotrypsin, and thiol metalloproteinase insulin-degrading... 

The pancreatic serine proteases trypsin, ch)unotrypsin, and elastase all hydrolyze peptide bonds. These enz)mies are the result of divergent evolution in which a single ancestral gene first duplicated and then each copy evolved individually. They have similar primary structures, sirtrilar tertiary structures (Figure 20.13), and virtually identical mechanisms of action. However, as a result of evolution, these enzymes all have different specificities ... 

Serine proteases Trypsin, chymolrypsin. elastasc, thrombin, plasminttgen, li.s.sue plasminogen activator Ser www.biochcm.wustl.edu/ protcase... 

The serine residue at position 195 is required for the activity of chymotrypsin in this respect, chymotrypsin is typical of a class of enzymes known as serine proteases. Trypsin and thrombin, mentioned previously, are also serine proteases (see the Biochemical Connections box on page 193). The enzyme is completely inactivated when this serine reacts with diisopropylphosphofluori-date (DIPF), forming a covalent bond that links the serine side chain with DIPF. The formation of covalently modified versions of specific side chains on proteins is called labeling it is widely used in laboratory studies. The other serine residues of chymotrypsin are far less reactive and are not labeled by DIPF (Figure 7.12). 

FIGURE 24.18 The catalytic triad in this serine protease (trypsin) is highlighted using the ball-and-stick model format for aspartic acid 52 (yellow-green), histidine 102 (purple), and serine 195 (red). A phosphonate inhibitor bound at the active site is shown in tube format. (This image and... 

Target class Serine protease (trypsin-like) D ydrogenase Immunoglobulin DNA polymerase Protein Ser/Thr kinase... 

Native ovoflavoprotein (49 kDa, pf=5.1) has, as does ovomucoid, certain antinutritional effects, as it inhibits serine proteases (trypsin, chymotrypsin and also microbial proteases) and has antiviral activity. Ovomacroglobulin (ovostatin) is an inhibitor of serine, cysteine, thiol and metalloproteases and shows antimicrobial activity. Some antinutritional effects are also seen in the basic glycoprotein avidin in raw egg white (relative molecular weight of the monomer is 15.6 kDa). It contains four identical subunits (pf = 9.5), each of which binds one molecule of biotin to give an unavailable complex. However, the denatured avidin, for example in hard-boiled eggs, does not interact with biotin. The interaction of riboflavin with flavoprotein (32 kDa, pf = 4.0) has, on the contrary, a positive influence on vitamin stability. Cystatin acts as cysteine protease inhibitor, and shows antimicrobial, antitumor and immunomodulating activities. 

Figure 2.33 shows the map for elastase and chymotrypsin. Rose (1979) developed an algorithm approach that requires only X-ray atomic coordinates. In his approach, the three-dimensional problem is reduced to an analysis in a plane by projection of the C position onto a disclosing plane. According to this procedure, domains are iteratively decomposed into sub-domains. A method for recognition of domains in proteins was also developed by Wodak and Janin (1980). Two continuous domains were observed in the structure of serine proteases, trypsin, chymotrypsin, and elastase (Hartley and Shotton, 1971 Blow and Steitz, 1970 Birktoft and Blow, 1972 ... 

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