Conformation amino acid residue

All valence electron MO calculations have been extended to the prediction of amino acid residue conformations. The approach has generally been to consider a model compound, such as an N-acylamino acid amide to simulate the mid-chain residue. Beginning with three independent studies reported in 1969 ( 56—58) a number of amino acid residue conformations have been predicted to date from all valence MO methods. Specific examples of amino acid residues studied, with references in order of appearance in the literature are glycine (56-59), alanine (56, 57, 59), phenylalanine (57), proline (57, 60), hydroxyproline (60), serine (61, 62), isoleucine (61, 88), valine (61,88), threonine (62), leucine (61,88), arginine (N-terminal) (63), arginine (C-terminal) (63), arginine side... 

In this way each amino acid residue is associated with two conformational angles and y. Since these are the only degrees of freedom, the conformation of the whole main chain of the polypeptide is completely determined when the ([) and y angles for each amino acid are defined with high accuracy. 

In complexes with Cro, the overall bend and twist of the DNA are similar to those in the repressor complexes, but there is a significant difference in the local structure of two of the nucleotides in each half-site. Binding of 434 Cro or repressor fragment thus imposes a distinct local structure (Figure 8.13), as a result of differences in both the identity and conformations of various amino acid residues that interact with the DNA. The DNA conformational details are significant for the relative affinities of Cro and repressor for various sites, as we describe in a later section. 

As noted, hemoglobin is an tetramer. Each of the four subunits has a conformation virtually identical to that of myoglobin. Two different types of subunits, a and /3, are necessary to achieve cooperative Oa-binding by Hb. The /3-chain at 146 amino acid residues is shorter than the myoglobin chain (153 residues), mainly because its final helical segment (the H helix) is shorter. The a-chain (141 residues) also has a shortened H helix and lacks the D helix as well (Figure 15.28). Max Perutz, who has devoted his life to elucidating the atomic structure of Hb, noted very early in his studies that the molecule was... 

A model for the allosteric behavior of hemoglobin is based on recent observations that oxygen is accessible only to the heme groups of the a-chains when hemoglobin is in the T conformational state. Perutz has pointed out that the heme environment of /3-chains in the T state is virtually inaccessible because of steric hindrance by amino acid residues in the E helix. This hindrance dis-... 

Before analyzing in detail the conformational behaviour of y9-peptides, it is instructive to look back into the origins and the context of this discovery. The possi-bihty that a peptide chain consisting exclusively of y9-amino acid residues may adopt a defined secondary structure was raised in a long series of studies which began some 40 years ago, on y9-amino acid homopolymers (nylon-3 type polymers), such as poly(/9-alanine) 3 [14, 15], poly(y9-aminobutanoic acid) 4 [16-18], poly(a-dialkyl-/9-aminopropanoic acid) 5 ]19], poly(y9-L-aspartic acid) 6 ]20, 21], and poly-(a-alkyl-/9-L-aspartate) 7 [22-36] (Fig. 2.1). 

The conformational preferences of mixed /9-peptides containing both /9 - and /9 -amino acid residues in their sequence differ markedly from that of the corresponding homopolymers consisting exclusively of /9 - or /9 -amino acid residues. Several types of mixed /9-peptides have been investigated including block peptides constructed with triads of /9 -amino acid residues and triads of /9 -amino acid residues (e.g. 93) [104,161], as well as alternating peptides of jf lff type (e.g., 72,... 

This effect is particularly well documented for y - and -amino acid residues [217, 218] which in several natural products (bleomycin A2 [219], calyculins [220]) have been shown to play a substantial role in the pre-organization of the whole molecule into its bioactive conformation. For example, changes in the substitution pattern of the y-amino acid linker in bleomycin A2 result in reduced DNA cleavage efficiency [219]. In the case of y-peptides, changing the relative configuration like or unlike of y " -amino acids has been used as a strategy to generate different local conformations (Fig. 2.34) suitable either for the construction of helices [201] or turns ]202-204]. 

Optimal pre-organization of the y-peptide backbone towards the formation of open-chain turn-like motifs is promoted by unlike-y " -amino acid residues. This design principle can be rationalized by examination of the two conformers free of syn-pentane interaction (f and II", Fig. 2.34). Tetrapeptide 150 built from homo-chiral unlike-y -amino acid building blocks 128e has been shown by NMR experiments in pyridine to adopt a reverse turn-like structure stabilized by a 14-mem-bered H-bond pseudocycle [202] (Fig. 2.37 A). 

While conformation II (Fig. 2.34) of Uke-y -amino acids is found in the 2.614-helical structure, conformation I, which similarly does not suffer from sy -pen-tane interaction, should be an appropriate alternative for the construction of sheet-like structures. However, sheet-like arrangement have not been reported so far for y-peptides composed of acyclic y " -amino acid residues. Nevertheless, other conformational biases (such as a,/9-unsaturation, cyclization between C(a) and C(y)) have been introduced into the y-amino acid backbone to restrict rotation around ethylene bonds and to promote extended conformation with formation of sheets in model peptides. Examples of such short chain y-peptides forming antiparallel (e.g. 152 [208]) and parallel (e.g. 153-155 [205, 208]) sheet-hke structures are shown in Fig. 2.38. 

---