Mixed P-sheets

Figure 2.7 (a) Illustration of the twist of (3 sheefs. Befa sfrands are drawn as arrows from the amino end to the carboxy end of the p strand in this schematic drawing of fhe protein thioredoxin from E. coli, fhe sfrucfure of which was defermined in the laboratory of Carl Branden, Uppsala, Sweden, fo 2.8 A resolution. The mixed p sheet is viewed from one of ifs ends, (b) The hydrogen bonds between the P strands in the mixed p sheet of fhe same profein. [(a) Adapfed from B. Furugren.]... 

Beta strands can also combine into mixed P sheets with some P strand pairs parallel and some antiparallel. There is a strong bias against mixed P sheets only about 20% of the strands inside the p sheets of known protein structures have parallel bonding on one side and antiparallel bonding on the other. Figure 2.7 illustrates how the hydrogen bonds between the p strands are arranged in a mixed P sheet. 

The most frequent of the domain structures are the alpha/beta (a/P) domains, which consist of a central parallel or mixed P sheet surrounded by a helices. All the glycolytic enzymes are a/p structures as are many other enzymes as well as proteins that bind and transport metabolites. In a/p domains, binding crevices are formed by loop regions. These regions do not contribute to the structural stability of the fold but participate in binding and catalytic action. 

Figure 4.19 Schematic and topological diagrams for the structure of the enzyme carboxypeptidase. The central region of the mixed p sheet contains four adjacent parallel p strands (numbers 8, 5, 3, and 4), where the strand order is reversed between strands 5 and 3. The active-site zinc atom (yellow circle) is bound to side chains in the loop regions outside the carboxy ends of these two p strands. The first part of the polypeptide chain is red, followed by green, blue, and brown. (Adapted from J. Richardson.)...

In this structure the loop regions adjacent to the switch point do not provide a binding crevice for the substrate but instead accommodate the active-site zinc atom. The essential point here is that this zinc atom and the active site are in the predicted position outside the switch point for the four central parallel p strands, even though these p strands are only a small part of the total structure. This sort of arrangement, in which an active site formed from parallel p strands is flanked by antiparallel p strands, has been found in a number of other a/p proteins with mixed p sheets. 

Upha/beta (a/p) structures are the most frequent and most regular of the pro-kein structures. They fall into three classes the first class comprises a central core of usually eight parallel p strands arranged close together like the staves pf a barrel, surrounded by a helices the second class comprises an open twisted parallel or mixed p sheet with a helices on both sides of the p sheet and Ihe third class is formed by leucine-rich motifs in which a large number of parallel p strands form a curved p sheet with all the a helices on the outside bfthis sheet. 

The C-terminal domain of phosducin is a five-stranded mixed p sheet with a helices on both sides, similar to the thioredoxin fold of disulfide iso-merase DsbA described in Chapter 6. Despite significant sequence homology to thioredoxin, the phosducin domain, unlike other members of this family. 

Unlike the Ciy proteins, Cyt toxins have a much broader toxicity spectrum. They are able to lyse a wide range of cell types in vitro, corresponding to the fact that Cyt proteins are structurally and functionally distinct from Cry toxins. To date, 18 cyt genes have been identified, and most of them were isolated from dipteran-active B. thuringiensis. X-ray crystallography of Cyt2A revealed that this toxin consists of a single domain, in which two outer layers of a-helices wrap around mixed p-sheets [34]. 

AU the transferrins crystalhzed to date share a couunon structure, an example of which is shown in Figure 3. The protein has two structurally homologous lobes of roughly 330 residues each, with a high sequence identity between them. Each lobe comprises two domains with a central mixed p-sheet surrounded by o -hehces. Between the domains is a cleft in which the metal ion binding site contained in each lobe is situated. One ferric ion binds to each site, with a carbonate ion binding concomitantly with each metal. 

The central, catalytic domain of ASV IN is a five-stranded mixed P-sheet flanked by five a-helices. The active site is characterized by the presence of the D,D(35)E motif of three carboxylate-containing amino acids, the last two of which... 

FIGURE 3.11 The hydrogen bonds between the p-strands in the mixed p-sheet of thioredoxin from E. coli. From Branden and Tooze, 1991. 

The crystal structures of three cohesins, two from C. thermocellum and one from C. cellulolyticum, have been reported (7-9). The cohesin domains form a nine-stranded P sandwich with a jelly-roll topology. The P sandwich results from the association of a four-stranded antiparallel P sheet, and a five-stranded mixed P sheet, stabilized by a hydrophobic core. The two P sheets are composed of strands 8,3,6,5 and strands 9,1,2,7,4 respectively. In addition, the three-dimensional structure of one dockerin (from the family-48 C. thermocellum cellulosomal enzyme, CelS) was solved by NMR spectroscopy (70). The dockerin structure consists of two Ca -binding loop-helix motifs connected by a linker. 

T. Asakura, M. Okonogi, Y. Nakazawa, K. Yamauchi, Stmcmral analysis of alanine tripeptide with antiparaUel and parallel P-sheet structures in relation to the analysis of mixed p-sheet stmctures in Sarnia cynthia ricini silk protein fiber using solid-state NMR spectroscopy, J. Am. Chem. Soc. 128 (2006) 6231-6238. 

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