A/p sheets

Figure 2.5 Schematic illustrations of antiparallel (3 sheets. Beta sheets are the second major element of secondary structure in proteins. The (3 strands are either all antiparallel as in this figure or all parallel or mixed as illustrated in following figures, (a) The extended conformation of a (3 strand. Side chains are shown as purple circles. The orientation of the (3 strand is at right angles to those of (b) and (c). A p strand is schematically illustrated as an arrow, from N to C terminus, (bj Schematic illustration of the hydrogen bond pattern in an antiparallel p sheet. Main-chain NH and O atoms within a p sheet are hydrogen bonded to each other.

Figure 2.14 shows examples of both cases, an isolated ribbon and a p sheet. The isolated ribbon is illustrated by the structure of bovine trypsin inhibitor (Figure 2.14a), a small, very stable polypeptide of 58 amino acids that inhibits the activity of the digestive protease trypsin. The structure has been determined to 1.0 A resolution in the laboratory of Robert Huber in Munich, Germany, and the folding pathway of this protein is discussed in Chapter 6. Hairpin motifs as parts of a p sheet are exemplified by the structure of a snake venom, erabutoxin (Figure 2.14b), which binds to and inhibits... 

Figure 2.21 Two sequentially adjacent hairpin motifs can be arranged in 24 different ways into a p sheet of four strands, (a) Topology diagrams for those arrangements that were found in a survey of all known structures in 1991. The Greek key motifs in (1) and (v) occurred 74 times, whereas the arrangement shown in (viii) occurred only once, (b) Topology diagrams for those 16 arrangements that did not occur in any structure known at that time. Most of these arrangements contain a pair of adjacent parallel P strands.

Each repeat forms a right-handed P-loop-a structure similar to those found in the two other classes of a/p structures described earlier. Sequential p-loop-a repeats are joined together in a similar way to those in the a/P-bar-rel stmctures. The P strands form a parallel p sheet, and all the a helices are on one side of the P sheet. However, the P strands do not form a closed barrel instead they form a curved open stmcture that resembles a horseshoe with a helices on the outside and a p sheet forming the inside wall of the horseshoe (Figure 4.11). One side of the P sheet faces the a helices and participates in a hydrophobic core between the a helices and the P sheet the other side of the P sheet is exposed to solvent, a characteristic other a/p structures do not have. 

We have described a general relationship between structure and function for the a/p-barrel structures. They all have the active site at the same position with respect to their common structure in spite of having different functions as well as different amino acid sequences. We can now ask if similar relationships also occur for the open a/p-sheet structures in spite of their much greater variation in structure. Can the position of the active sites be predicted from the structures of many open-sheet a/p proteins ... 

In almost every one of the more than 100 different known a/p structures 1 of this class the active site is at the carboxy edge of the p sheet. Functional residues are provided by the loop regions that connect the carboxy end of the strands with the amino end of the a helices. In this one respect a fun-I damental similarity therefore exists between the a/p-barrel structures and the I open a/p-sheet structures. 

Cohen, F.E., Sternberg, M.J.E., Taylor, W.R, Analysis and prediction of the packing of a-helices against a p-sheet in the tertiary structure of globular proteins. 

The second protein in the membrane of influenza vims, neuraminidase, does not belong to any of these three groups of barrel structures. Instead, it forms a propeller-like structure of 24 p strands, arranged in six similar motifs that form the six blades of the propeller. Each motif is a p sheet of 4 up-and-down-connected p strands. The enzyme active site is formed by loop regions on one side of the propeller. 

Figure 16.18 A dimer is the basic unit that builds up the capsid of bacteriophage MS2. The two subunits (red and biue) are arranged so that the dimer has a p sheet of 10 antiparaliel strands on one side and the hairpins and a heiices on the other side. The heiices from one subunit pack against p strands from the other subunit and vice versa. (Adapted from a diagram provided by L. Liljas.)...

The augmentation of a p sheet in one protein by a strand emanating from another is a mode of protein association not restricted to viral shells. Small domains involved in intracellular signal transduction bind to "arms" of other proteins by presenting the edge of a sheet on which those arms can form an additional strand. 

The capsids of polyoma virus and the related SV40 have icosahedral symmetry, with 72 pentameric assemblies of the major capsid protein. The pentamers are linked to their neighbors by flexible arms, with a p strand that augments a p sheet in the invaded pentamer. These flexible arms allow the pentamers to be linked together with both fivefold and sixfold symmetry. 

TBP-TATA box complexes are known A p sheet in TBP forms the DNA-binding site TBP binds in the minor groove and induces large structural changes in DNA The interaction area between TBP and the TATA box is mainly hydrophobic Functional implications of the distortion of DNA by TBP... 

Polymer supported xanthene derivatives have been used in the solid phase synthesis of 1-aminophosphinic acids, RCH(NH2)PH(0)0H, <%TL1647> and of C-terminal peptide amides <96JOC6326>. Xanthene units also feature in crown ethers <96JCS(P2)2091>, calixarenes <96JOC5670> and in a flexible template for a P-sheet nucleator <96JOC7408>. 

Waals interactions with the PI Cys, and also located basic Arg and Lys residues in position to interact with the P6 acidic residue. More detail of the binding of the N-terminal (i.e., P residues) part of the substrate was subsequently inferred from NMR studies showing a p-sheet interaction between this N-terminal segment of the substrate and enzyme largely confined to within the C-terminal p-barrel (Cicero et al. 1999). 

Alternative approaches to imprint peptides via strong monomer template association have recently been reported, although no results of the chromatographic application of these phases have been shown. Strong complexation inducing a p-sheet conformation was possible using a designed functional monomer (21) [71]. Peptides... 

Figure 11.2 Polypeptide chains held together by hydrogen bonds, indicated by dashed lines, in a configuration called a P sheet, (a) The antiparallel P pleated sheet, (b) The parallel P pleated sheet. (Illustration, Irving Geis/Geis Archive Trust. Copyright Howard Hughes Medical Institute. Reproduced with permission.)...

Lipases belong to the subclass of serine hydrolases, and their structure and reaction mechanism are well understood. Their common a/p-hydrolase enzyme fold is characterized by an a-helix that is connected with a sharp turn, referred to as the nucleophilic elbow, to the middle of a P-sheet array. All lipases possess an identical catalytic triad consisting of an Asp or Gin residue, a His and a nucleophilic Ser [14]. The latter residue is located at the nucleophilic elbow and is found in the middle of the highly conserved Gly—AAl—Ser—AA2—Gly sequence in which amino acids AAl and AA2 can vary. The His residue is spatially located at one side of the Ser residue, whereas at the opposite side of the Ser a negative charge can be stabilized in the so-called oxyanion hole by a series of hydrogen bond interactions. The catalytic mechanism of the class of a/P-hydrolases is briefly discussed below using CALB as a typical example, since this is the most commonly applied lipase in polymerization reactions [15]. 

For an octapeptide sequence taken from the C-terminal residues of the Alzheimer s Ap-peptide Lansbury et al. identified a large intensity enhancement for 13C-labeled modes that was sequence-dependent and assessed as largely due to interstrand dipole-coupling.1207,2351 Mendelsohn et al. found a similar effect by double labeling on alternate sites a peptide that formed a P-sheet-like structure in methanol.12501 Subsequent theoretical modeling showed this latter intensity enhancement to be a function of forming extended, flat, anti-parallel P-sheet structures,12511 and the overall effect to be highly position sensitive.12451... 

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