Valyl residue

The techniques mentioned here provide a basic approach to the study of hemoglobinopathies since the Identification of many variants Is dependent upon their net charge. However, certain changes In the tertiary structure of a hemoglobin variant may also alter Its electrophoretic behavior. This Is well documented for many unstable variants such as for Hb-K51n which migrates more slowly than Hb-A but In which the neutral valyl residue In position 398 Is replaced by the neutral methlonyl residue. It should also be mentioned that differences In the level of heme oxidation will cause differences In the electrophoretic mobility. 

This enzyme [EC 3.4.22.17] is an intracellular, nonlyso-somal member of the peptidase family C2. The enzyme catalyzes the calcium ion-dependent hydrolysis of peptide bonds with preference for Tyr-Xaa, Met-Xaa, or Arg-Xaa with a leucyl or valyl residue at the P2 position. There are two main types of calpain. One has a high calcium sensitivity in the micromolar range and is called (,-calpain or calpain I. The other calpain has a low calcium sensitivity in the millimolar range and is called m-calpain or calpain II. Forms of calpain exhibiting intermediate calcium sensitivity also exist. 

This enzyme [EC 3.4.21.12] catalyzes the hydrolysis of peptide bonds in proteins, especially at peptide bonds adjacent to alanyl and valyl residues of bacterial cell walls, elastin, and other proteins. The enzyme is a member of the peptidase family S2A. See also Chymotrypsln Catalytic Triad... 

This endopeptidase [EC 3.4.22.2], a member of the Cl peptidase family hydrolyzes peptide bonds in proteins, exhibiting a broad specificity for those bonds. There is a preference for an amino acyl residue bearing a large hydrophobic side chain at the P2 position and the enzyme does not accept a valyl residue at Pi. 

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. 

Fig.1 8. Structure of the heme group in hemoglobin and the positions of the yj-and y2-CH3 groups of the Ell valyl residue and the C-2-H of the E7 histidyl residue in the CO and oxy forms of the a chain of Hb A. The positions for the CO form (full circles) were calculated from the X-ray coordinates for the a chain of HbCO A (Baldwin, 1980), whereas the approximate positions for the oxy form (broken circles) were calculated from our NMR data and theoretical ring-current calculations. [From Dalvit and Ho (1985)].

P, J. Milburn, Y. C. Meinwald, S. Takahashi, T. Ooi, and H. A. Scheraga. Int. /. Pept. Protein Res., 31, 311 (1988). Erratum ibid., 31, 587 (1988). Chain Reversals in Model Peptides Studies of Cystine-Containing Cyclic Peptides. II. Effects of Valyl Residues and Possible / -to-(< + 3) Attractive Ionic Interactions on Cyclization of [Cys1], [Cys ] Hexapeptides. 

HC3 (146) and the y-carboxyl side chain of Asp FGl (94) p whereas similar bridges between a-amino groups of the amino-terminal valyl residues and the a-carboxyl group of the carboxy-terminal arginyl residues are responsible for the remainder of the effect. 

The importance of the amino terminal valyl residue for the binding of 2,3-DPG is indicated by the observation that hemoglobins with blocked amino terminal residues, such as the minor human hemoglobin Aic (B77) and one of the hemoglobins of the cat (Tl), and hemoglobins that lack this residue and thus have p chains with only 145 residues, such as the hemoglobin of sheep (B79), do not combine with this organic phosphate. 

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 the case of the valyl residue PCILO predicts a global minimum where our method predicts a maximum. As seen in Figure 11 the conformation of the valyl residue in globular proteins occupies the minimum regions located by CONFOR and what would be a local minima in the PCILO method. The barrier between = 270,... 

Figure 11. Comparison of the energy contours calculated for the valyl residue (see Figure 4 for...

Figure 12. View of the valyl residue showing the interaction between the carbonyl and one of the hydrogens on the isopropyl. This conformation is the minimum energy conformation as calculated by PCILO (Figure 11).

Figure 13. Contour map for the valyl residue calculated using CON FOR. This map was generated by allowing the isopropyl group to relax and seek a minimum...

C15H32N7O7P, Mr 453.44, hygroscopic powder, mp. 157-161 C (decomp.), [a] +14.7° (H O). An unusual iV-L-arginy Iphosphonic acid hydrazide from cultures of Streptomyces lavendofoliae. It also occurs without the L-valyl residue as F. B (C,oH23N60gP, Mr 354.30). The F. have antifungal activities. 

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). 

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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