Beta-strand conformation

Yang, J., Gabrys, C. M. and Weliky, D. P. (2001) Solid-state nuclear magnetic resonance evidence for an extended beta strand conformation of the membrane-bound HIV-1 fusion peptide. Biochemistry, 40, 8126-8137. 

Peptidomimetic approaches are heavily used to build protease inhibitor scaffolds. Selective protease inhibitors are quite straightforward to be obtained because of the substrate variety and specificity of the proteases. However, the concept of privileged scaffolds does not carry far for proteases. The unifying element in protease substrates is the extended beta-strand conformation that allows interactions with four to six subpockets in the protease active site (69). Mimics for this conformation have been developed but they still lack universal applicability for the transfer into clinical application (70). 

Aggeli A, Boden N, Cheng YL, Findlay JB, Knowles PF, Kovatchev P, Turnbull PJ. Peptides modeled on the transmembrane region of the slow voltage-gated IsK potassium channel structural characterization of peptide assemblies in the beta-strand conformation. Biochemistry 1996 35 16213-16221. 

If the sequence of a protein has more than 90% identity to a protein with known experimental 3D-stmcture, then it is an optimal case to build a homologous structural model based on that structural template. The margins of error for the model and for the experimental method are in similar ranges. The different amino acids have to be mutated virtually. The conformations of the new side chains can be derived either from residues of structurally characterized amino acids in a similar spatial environment or from side chain rotamer libraries for each amino acid type which are stored for different structural environments like beta-strands or alpha-helices. 

Fig. 1. Schematic diagram of nuclease A131A in the folded conformation. The alpha helices and beta strands are labeled. NMR analysis suggests the two turns and one helix in black are modestly populated in the denatured state, whereas the shaded helix is slightly populated. Strands / l-/ 2-/ 3 form an extended structure about which littie is known. Reproduced from Barron, L. D., Hecht, L., Blanch, E. W., and Bell, A. F. (2000). Prog. Biophys. Mol Chem. 73, 1-49. 2000, with permission from Elsevier Science.

Antzutkin, O. N., Balbach, J. J., and Tycko, R. (2003). Site-specific identification of nonbeta-strand conformations in Alzheimer s beta-amyloid fibrils by solid-state NMR. Biophys.J. 84, 3326-3335. 

The steric relations of residues nearby in the primary structure which give rise to local regularities of conformation. These structures are maintained by hydrogen bonds between peptide bond carbonyl oxygens and amide hydrogens. The major secondary structural elements are the helix and the beta strand. (Characteristic bond type hydrogen.)... 

Thioredoxin from E. coli has been studied extensively using biochemical, spectroscopic and X-ray diffraction techniques. The protein consists of a single polypeptide chain of 108 amino acid residues of known sequence. The protein has been cloned and expressed. Thioredoxin of E. coli is a compact molecule with 90% of its residues in hehces, beta-strands or reverse turns. This protein transports electrons via an oxidation-reduction active disulfide". The oxidized form thioredoxin-(S2) is reduced to thioredoxin-(SH)2. In particular, this protein was found to participate in the reduction of ribonucleotides to deoxyribonucleotides. In Fig. 1, the optimized stracture is shown with a carbon backbone for clarity only. The molecule consists of two conformational domains, connected by two helices. The beta-sheet forms the core of the molecule packed on either side by clusters of hydrophobic residues. Helices form the external surface. We used a crystal stracture of the oxidized form of thioredoxin from Escherichia coli that has been refined by the stereochemically restrained least-squares procedure at 1.68 A resolution". ... 

Analysis by NMR of recombinant elk PrP revealed that the loop region connecting between the second beta-strand ((32) and the second alpha helix (7.2), (32-7.2 loop, encompassing residues from 165 to 175 (all the codon numberings of PrP below conform numbering of corresponding residues in human PrP), was outstandingly... 

Org. Lett. 2000, 2, 2037-2040 A.B. Smith, T.P. Keenan, R.C. Holcomb, P.A. Sprengeler, M.C. Guzman, J.L. Wood, P.J. Carroll, R. Hirschmann, Design, synthesis, and crystal-structure of a pyrrolinone-based peptidomimetic possessing the conformation of a beta-strand - potential application to the design of novel inhibitors of proteolytic-enzymes, J. Am. Chem. Soc. 1992, 114, 10672-10674 A.B. Smith, L.D. Cantin, A. Pasternak, L. Guise-Zawacki, W.Q. Yao, A.K. Charnley, J. Barbosa, P.A. 

Several studies have confirmed that beta-amyloid peptides undergo structural transitions to form mobile oligomers that are composed of a particular aggregation-prone conformation of the peptide. Once the oligomers exceed critical size, they nucleate to form protofilaments which finally transform to crossbeta sheets or fibrils that are responsible for the formation of extracellular amyloid plaques. The tendency to form beta-strands is due to its ability to stabilize the beta-turn by a salt bridge between residues aspartic acid-23 and lysine-28 and the hydrophobic region. 

From WAXS and SAED data of both ProNectin F lyophilized powder and sprayed fibrils, the current model indicates that ProNectin F crystallizes into a chain folded pleated sheet of beta strands (Anderson et a/. 1994). The strands are oriented antiparallel. The beta strands are not fully extended, but have a more compressed crankshaft conformation. This conformation agrees with the predicted conformation of unoriented silk fibroin protein, the Silk I structure (Lotz and Keith 1971). The crystal dimension in the c direction (along the peptide backbone) is consistent with a theoretical length of 11.6 nm for nine SEP blocks (54 amino acids) in this conformation. This predicts that the width of the ProNectin F tile is controlled at least in part by the number of amino acids in the silklike block domains. 

Ramachandran R, Tweten RK, Johnson AE. Membrane-dependent conformational changes initiate cholesterol-dependent cytolysin oligomerization and intersubunit beta-strand alignment. Nat Struct Mol Biol. 2004 11(8) ... 

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.

We have completed several structures each of NPl, NP2, and NP4 (31, 46 9, 110). These structures reveal the Rhodnius nitrophorins to have a fold dominated by an eight-stranded antiparallel beta-barrel, as shown in Fig. 15, and to rely on a remarkable ligand-induced conformational change for NO transport, described later. The structures confirm that the nitrophorins are completely unrelated to the globins, the only other heme-based gas transport proteins whose structures are known. Rather, their fold places them in the lipocalin family, for which several other examples are known (111-113). Our initial nitrophorin structure was of NPl and was determined using standard MIR and... 

Secondary structure refers to regularities or repeating features in the conformation of the protein chain s backbone. Four major types of secondary structure in proteins are (1) the alpha (a) helix, formed from a single strand of amino acids (2) the beta (P) sheet, formed from two or more amino acid strands (from either the same chain or from different chains) (3) the beta (P) bend or reverse turn, in a single strand and (4) the collagen helix, composed of three strands of amino acids. 

The beta-l,3-glucans are dramatically different from the glucans described so far. This polymer is extremely flexible, and occurs in many instances in nature. The polymer goes by the names of curdlan, pachyman, laricinan, schleroglucan, paramylon, lentinan, laminarin, callose and schizophylan. The prevalent form appears to be a triple helix, with n > 6 and b 0.3 nm for each of the three strands ( ). If triacetate derivatives are made, n > 6 and h = 0.31 to 0.36 nm (10). The acetate helices are single. Of some interest is the lack of allowed 2-fold conformations on the n-b map (Figure 5). The allowed zones close up when n = 20 or so, but some small adjustments in the monomer shape could allow an infinite number of monomeric units per helix repeat. 

Residues 386-433 and 690-802 form a small, probably structural domain. The next two domains, residues 434-691 and 804-1022, are methyltransferase domains, and their folds are two different variations on the "universal" methyltransferase fold (Fig. 2D), a beta sheet with defined strand order and directionality sandwiched between alpha helices ". Soaking experiments with SAH confirm that for both domains the SAM binding site coincides with that in other methyltransferases. For the more N-terminal methyltransferase domain, SAH binding is accompanied by a conformational change, in which residues 519-524 and 579-587 rearrange in order to participate in binding. While each methyltransferase domain binds SAM independently, experiments indicate that 7N methyltransfer occurs only in X2 pentamers and not in monomers. (Equivalent experiments for 2 0 methyltransfer have not been reported.)... 

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