Regular secondary structures

SD Rufino, LE Donate, LHI Canard, TL Blundell. Predicting the conformational class of short and medium size loops connecting regular secondary structures Application to comparative modeling. I Mol Biol 267 352-367, 1997. 

Figure 1.1 The amino acid sequence of a protein s polypeptide chain is called Its primary structure. Different regions of the sequence form local regular secondary structures, such as alpha (a) helices or beta (P) strands. The tertiary structure is formed by packing such structural elements into one or several compact globular units called domains. The final protein may contain several polypeptide chains arranged in a quaternary structure. By formation of such tertiary and quaternary structure amino acids far apart In the sequence are brought close together in three dimensions to form a functional region, an active site.

Figure 2.8 Adjacent antiparallel P strands are joined by hairpin loops. Such loops are frequently short and do not have regular secondary structure. Nevertheless, many loop regions in different proteins have similar structures, (a) Histogram showing the frequency of hairpin loops of different lengths in 62 different proteins, (b) The two most frequently occurring two-residue hairpin loops Type I turn to the left and Type II turn to the right. Bonds within the hairpin loop are green, [(a) Adapted from B.L. Sibanda and J.M. Thornton, Nature 316 170-174, 1985.]...

The recognition that short chain / -peptides can form regular secondary structures initially came from detailed conformational analysis of y9 -peptides 1 and 66 (which incorporates a central (2S,3S)-3-amino-2-methylbutanoic acid residue) by NMR in pyridine-d5 and CD3OH [10, 103, 164] and homooUgomers (as short as four residues) of trons-2-amino-cyclohexanecarboxyhc acid (trans-ACHC) (e.g. hex-amer 2 for the (S,S) series) by NMR and X-ray diffraction [6, 126, 159]. 

Recently, a / -dodecapeptide was found to display a CD spectrum in water which was very similar to that assigned to the 12/10-helix, with a single maximum near 200 nm. Careful NMR analysis however, revealed a predominantely extended conformation without regular secondary structure elements [174]. This result stresses that the CD signature assigned to the 12/10-structure might not be unique and again (see Section 2.2.3.1) that CD spectra must be interpreted with caution. 

As mentioned above, which of the sequential NOEs d j, d j, and dj j is observed depends on the conformation of the backbone for the residues involved. Repetition of a particular type of connectivity for a sequence of amino acids often occurs in regions of regular secondary structure (19). For example a stretch of d jj-type NOEs is a signature of extended conformation, whereas a sequence of dj j -type NOEs is characteristic of helical conformation. Turns, on the other hand, are characterized by short, distinct patterns of dj j and d j connectivities. 

A model of a Pn helix formed by alanine side chains is illustrated for reference in Figure 13B (see color insert), while Figure 13A illustrates the common occurrence of the Pn backbone conformation among residues outside regions of regular secondary structure (Kleywegt and Jones, 1996 Serrano, 1995 Stapley and Creamer, 1999) in protein structures from the Protein Data Bank. 

This discussion puts us in a position to define a set of structural and evolutionary objects the tracing of whose history via homology, as implied by sequence similarity, is the primary aim of sequence analyses. The simple view of protein folding produces a small set of structural components to consider. This is the set of regular secondary structures the amphipathic a helix, the transmembrane or hydrophobic a. helix, the... 

An analysis of metal binding to peptide carbonyl groups (Chakrabarti, 1990), mainly calcium ions in protein crystal structures, shows that the cations tend to lie in the peptide plane near the C=0 bond direction. Generally, this binding occurs in turns in proteins or in regions with no regular secondary structures. Ca---0 distances range from 2.2 to 2.5 A, and metal ions do not deviate by more than 35° from the peptide plane. Thus, metal ions in proteins do not, Chakrabarti observed, bind in lone-pair directions. 

Ribonuclease-S can be separated into S-peptide [residues 1-20 (21)] and S-protein [residues 21 (22)-124] by precipitation with trichloroacetic acid 73) or better, Sephadex chromatography in 5% formic acid 83). The best preparations of these components show no detectable hydrolytic enzymic activity and little if any transphosphorylation activity (see Section VI). Isolated S-peptide appears to have no regular secondary structure 83, 84) or 10-20% helicity 85, 86). (These slightly different interpretations are based on almost identical CD data.) When equimolar amounts of S-protein and S-peptide are mixed at neutral pH and room temperature or below, essentially full catalytic activity is recovered 73, 87). A schematic diagram is shown in Fig. 7. For a detailed summary of the preparative procedures see Doscher 88). 

Imino structure—for example, proline (P), whose amino group forms imino ring with the rigid conformation therefore its presence disrupts the formation of regular secondary structures. 

The regular secondary structures, a helices and /i sheets, are connected by coil or loop regions of various lengths and irregular shapes. A variant of the loop is the f> turn or reverse turn, where the polypeptide chain makes a sharp, hairpin bend, producing an antiparallel / turn in the process. 

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