Three-dimensional structures elastase

This is nicely illustrated by members of the chymotrypsin superfamily the enzymes chymotrypsin, trypsin, and elastase have very similar three-dimensional structures but different specificity. They preferentially cleave adjacent to bulky aromatic side chains, positively charged side chains, and small uncharged side chains, respectively. Three residues, numbers 189, 216, and 226, are responsible for these preferences (Figure 11.11). Residues 216... 

Shotton, D.M., Watson, H.C. Three-dimensional structure of tosyl-elastase. Nature 225 811-816, 1970. 

Figure 12-9 Alpha-carbon diagram of the three-dimensional structure of pancreatic elastase. A principal structural feature is a pair of p cylinders.

The amino acid sequence of the enzyme is homologous with those of the pancreatic enzymes and has been shown by model building to be compatible with a chymotrypsin-like three-dimensional structure and catalytic site (36). The homology in sequence is particularly well marked around His-57. The enzyme s catalytic properties are virtually indistinguishable from those of pancreatic elastase. 

Much but not all of this work has dealt with proteins the three-dimensional structures of which have been determined by x ray lysozyme, ribonuclease, myoglobin, hemoglobin, cytochrome C, carboxy-peptidase, chymotrypsin, concanavalin, trypsin, elastase, and sub-tilisin. The principal nucleus has been the proton, but more recently 13 C has been studied by several groups. Other nuclei, such as 19 F, 31P, and 35Cl, have found limited application in special studies. 

The three-dimensional structure of many enzyme molecules, including hydrolytic enzymes such as lysozyme, chymotrypsin, ribonuclease, carboxypeptidase A, elastase, and papain, has been determined in recent years throu] the X-ray diffraction method, and the steric arrangement and function of amino acid residues at the active site has been elucidated (/). 

Fig. 2.34. Ribbon diagrams showing the three-dimensional structure of (a) chymotrypsin, (b) elastase (from Hartley and Shotton, 1971). The organization of these molecules into two domains is indicated in the drawings which also display the structural similarities between both enzymes. 

Fig. 10.5. Three-dimensional structure of elastase (according to Sawyer et a/., 1978) indicating the two domains. An arrow indicates the cleavage by trypsin (courtesy of H. C. Watson).

Elastin, a stmctural protein with mbber-like elastic properties. It is the main component of the elastic yellow connective tissue occurring, e.g., in the lungs and aorta. The amount of elastin is rather low in the inelastic white connective tissue of tendons. Elastin consists of 850-870 aa with a high content of Gly (27%), Ala (23%), Val (17%), and Pro (12%). It forms a three-dimensional network of fibers crosslinked by desmosine, lysinonor-leucine, and isodesmosine. It has been reported that elastin has an unanticipated regulatory function during arterial development, controlling the proliferation of smooth muscle and stabilizing arterial structure [L. Robert, W. Hornebeck (Eds.), Elastin and Elastases, Volume 1, CRC Press, Boca Raton, EL, 1989 D. R. Eyre et al, Annu. Rev. Biochem. 1984, 53, 717 D. Y. Li et al., Nature 1998, 393, 276]. 

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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