Amino acids threading

This section briefly reviews prediction of the native structure of a protein from its sequence of amino acid residues alone. These methods can be contrasted to the threading methods for fold assignment [Section II.A] [39-47,147], which detect remote relationships between sequences and folds of known structure, and to comparative modeling methods discussed in this review, which build a complete all-atom 3D model based on a related known structure. The methods for ab initio prediction include those that focus on the broad physical principles of the folding process [148-152] and the methods that focus on predicting the actual native structures of specific proteins [44,153,154,240]. The former frequently rely on extremely simplified generic models of proteins, generally do not aim to predict native structures of specific proteins, and are not reviewed here. 

Threading methods can assign amino acid sequences to known three-dimensional folds... 

Lathrop, R. FI. (1994). The protein threading problem with sequence amino acid interaction preferences is NP-complete. Protein Eng. 7, 1059—1068. 

Scientists carry out searches on databases. Each EST of interest can be compared with sequences in proteins, and the degree of match can be determined. A technique called threading is used. This involves using data on three-dimensional (3D) protein structure, coupled with knowledge of the physicochemical properties of amino acids, to determine if the amino acid sequence is likely to fold in the same way as a sequence for which the structure is known. In this way, more information about the putative target protein can be assessed. 

Figure 11 Unnatural amino acids to probe the inactivation mechanism of ion channel Kv1.4. OMeTyr or dansylalanine extends the side chain length of tyrosine, which impedes the inactivation peptide from threading through the side portal of the ion channel and abolishes the fast inactivation, as shown in the current-time curve in the bottom panel.

Silk is produced from the spun threads from silkworms (the larvae of the moth Bombyx mori and related species). The main protein in silk, fibroin, consists of antiparallel pleated sheet structures arranged one on top of the other in numerous layers (1). Since the amino acid side chains in pleated sheets point either straight up or straight down (see p. 68), only compact side chains fit between the layers. In fact, more than 80% of fibroin consists of glycine, alanine, and serine, the three amino acids with the shortest side chains. A typical repetitive amino acid sequence is (Gly-Ala-Gly-Ala-Gly-Ser). The individual pleated sheet layers in fibroin are found to lie alternately 0.35 nm and 0.57 nm apart. In the first case, only glycine residues (R = H) are opposed to one another. The slightly greater distance of 0.57 nm results from repulsion forces between the side chains of alanine and serine residues (2). 

Steinbrunn and Wenz recently reported poly(amide-CD rotaxane)s 53 via a very imaginative approach [90,91]. First, the CD was threaded on to an a,co-amino acid in water to give a pseudorotaxane monomer. An NMR study showed that two CD molecules were threaded per linear molecule for 11-aminoundecanoic acid. The X-ray powder pattern indicated that these rotaxanes stacked like channels in the solid state this provided the basis for solid state polymerization at 200°C to afford polyamide 53 with m/n=2 ... 

The synthesis was carried out using 125 Chiron Mimotopes Crowns (capacity 5.3 pmol each) derivatized with an Fmoc -Rink amide linker. The procedure was started with the formation of five strings by threading 25 crown units on Berkley Fire Line fishing line. Five Fmoc-protected amino acids were used in each coupling position as demonstrated in the flow diagram of the synthesis (Fig. 11). 

The most widely known ordered structure in polypeptides is the a-helix. When the repeating units are amino acid residues of l configuration, the a-helix is right-handed i.e., the chain backbone follows the pattern of the thread of a right-hand screw. Each turn of the helix is made up of 3.6 residues, so the helix is nonintegral. An exact repeat of the backbone structure occurs every 18 monomeric units. This repeat corresponds to five turns of the helix, with a linear translation along the axis of 27 A and a pitch of 5.4 A. The helix diameter, neglecting side chains, is about 6 A. 

A common thread that can link the ammonium and peptone catalyst poisoning results just described could be the Maillard reactions of amino acids with sugars (5). Recent studies have shown that the ammonium ion is highly reactive, more so than substituted versions (6). Its use as ammonium bicarbonate in developing flavoring compounds by Maillard reactions in extrusion cookers has been reported (7). It is likely that such reactions could occur at our processing conditions. We can speculate that such products could have acted as catalyst surface poisons, which might have been subsequently washed from the catalyst, before it was reused in its active form. 

The 3D-ID compatibility algorithm (Ito et ah, 1997) is applied to predict the secondary structures by threading at SSThread of DDBJ (http //www.ddbj.nig.ac.jp/ E-mail/ssthread/www service.html). Paste the query sequence (fasta format) into the sequence box, enter your e-mail address, and click the Send button. The e-mail returns the threading result reporting the amino acid sequence with the predicted secondary structures (H for a. helix, E for / strand, and C for coil or other). 

In a study of chiral dipeptide [2]rotaxanes it was found that the presence of an intrinsically achiral benzylic amide macrocycle near to the chiral center could induce an asymmetric response in the aromatic ring absorption bands [62], This induced circular dichroism (ICD) effect was stronger in apolar solvents (Fig. 9), where intercomponent interactions are maximized, showing a direct relationship to the tightness with which the macrocycle binds the chiral thread. Computer simulations showed that chirality is transmitted from the amino acid asymmetric center on the thread via the achiral macrocycle to the aromatic rings of the achiral C-terminal stopper. 

The ribosome structure is perhaps the most impressive natural rotaxane. Messenger RNA, as the rotaxane thread, is clamped by the ribosomal protein subunits which read each codon and transcribe it into a sequence of amino acids that are introduced by transfer RNAs to build up the desired protein. The importance of the ribosomes has been reflected in the number of Nobel Prize recipients associated with their discovery (Palade in 1974) and elucidation of their structures and functions (Ramakrishnan, Steitz and Yonath in 2009). 

---