Valyl amino acid residues

A particularly interesting set of calculations are those we performed on the glycyl and valyl amino acid residues. Pullman has reported work on both molecules (12). In order to compare our results we reproduced these calculations using the CONFOR module. Figure 10 shows a comparison of the maps for the glycyl residue. The dots on the maps represent known conformations of glycyl residues in globular proteins. 

Sometimes deletions of amino acid residues may have a profound influence on the physicochemical and functional properties of the variant. The deletion of valyl residue in position p 23 (B5), for instance, results in considerable changes in spectral absorption, in affinity for molecular oxygen, and in heat stability. The deletion of the five residues in Hb-Gun Hill is near the heme position, and heme will not bind to the altered p chain. However, when the deletion occurs near a terminus, as in Hb-Leiden, the effect is minimal. 

In most cases of formation of peptides containing d-amino acid, the L form of the amino acid is the substrate for the incorporating enzyme. In contrast, the free D-amino acid is ordinarily a poor substrate for the incorporation reaction. Whether the racemization occurs on the enzyme or afterwards remains to be determined in most cases. In the case of the D-valyl residue formed in penicillin, a tripeptide derivative containing L-valine is an intermediate, and the conversion is thought to occur by way of an a,/3-dehydro form of the valyl residue. 

In 1955, H. Brockmann and Schmidt-Kastner [15] isolated an antibiotic substance from extracts of Streptomyces fulvissimus. They named it valinomycin after valine having been found as the only amino acid in the acid-hydrolyzate. Since no amino group nor carboxyl group could be detected in the substance which was almost insoluble in water, a cyclic structure had to be assumed. Valinomycin has a macrocyclic molecular structure consisting of three identical tetradepsipeptide fragments with alternating peptide and ester bonds between D-a-hydroxyisovaleric acid, D-valine, L-lactic add, L-valyl residues (Fig. 10). 

Pepstatin is a low molecular weight, potent inhibitor specific for acid proteases with a value of about 10" M for pepsin. The chemical structure of pepstatin is essentially a hexapeptide which contains two residues of an unusual amino acid, 4-amino-3-hydroxy-6-methylheptanoic acid (statine). The complete structure of pepstatin is isovaleryl-L-valyl-L-valyl-statyl-L-alanyl-statine. 

Mechanistically, NCL is a two-step process, which is initiated by a reversible transthioesterification step followed by a spontaneous, irreversible S- to N-acyl transfer (Fig. 1). The reactivity is affected by several factors such as concentration of the reactants, temperature, pH, and choice of an appropriate thiol. Also the C-terminally thioes-terified amino acid at the ligation site has to be considered carefully [3]. In feet, NCL relies basically on an observation ofWieland et al., who first demonstrated the transfer of a valyl residue from a reactive thioester onto a cysteine under slightly basic conditions followed by a rearrangement and yielding a Val-Cys dipeptide [4]. 

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