Gly residue

Figure 48-15. Simplified scheme of the causation of achondroplasia (MIM 100800). In most cases studied so far, the mutation has been a G to A transition at nucleotide 1138. In a few cases, the mutation was a G to C transversion at the same nucleotide. This particular nucleotide is a real "hot spot" for mutation. Both mutations result in replacement of a Gly residue by an Arg residue in the transmembrane segment of the receptor. A few cases involving replacement of Gly by Cys at codon 375 have also been reported.

These results can be rationalized as follows. Cyclic imide formation is maximal with a Gly residue because of its minimal steric interference. In contrast, steric bulk (i.e., size and branching) of the C-flanking residue is the major factor decreasing the reactivity of Asn to form a succinimide. Residues with a functionalized side chain, namely serine, threonine, and histidine, behaved as exceptions to this rule (see above). 

In a follow-up study, the effect of introduction of achiral Gly residues into the Ala-peptide chain (di- and tripeptides) on the afforded enantiomer separations was thoroughly investigated [123]. One of the major findings was that the introduction of a Gly residue compromised the enantioselectivity in particular if the Gly residue was located at the /V-terminus. For example, a-values (for all-5/all-7 enantiomers) decreased in the order Ala-Ala > Ala-Gly > Gly-Ala for the DNB-protected dipeptide... 

HFC and HNC also differ with respect to their peptide and collagen specificities. Both HFC and HNC cleave all three a chains of types I, II and III collagens following the Gly residue of the partial sequences Gly-[Ile or Leu]-[Ala or Leu] in these collagens [91,92] at a single site located approximately three-fourths from the NH2-terminus. This single scission of these... 

Fig. 19. A plot of the root-mean-square (rms) deviation of backbone atoms between HO-1 molecules A and B in the asymmetric unit. There is a large deviation in the distal helix just above the heme. In molecule B the distal helix is farther from the heme, thereby providing a more open pocket. Such flexibility may be required for substrate binding and product release. The required flexibility is very likely due to the conserved Gly residues in the distal helix.

To analyze structure/function relationship of different elements within the GRR, we studied the function of different deletion and point mutants. The human pi05 GRR contains 19 Gly residues (out of 29 residues in total 376-GGGSGAGAGGGGMFGSGGGGGGTGSTGPG-404), two of which are interspaced by Ala (380-GAGAG-384). Deletion analysis revealed that only 6 (382-GAGGGGMFGS-391) Gly residues are sufficient to promote, at least partially, generation of p50. Importantly, the Ala residue is essential (16). 

CH, CH" remote correlations for Gly residues will show up in a position approximately mirror image to F = 0. 

Suggested preferred conformations can be fixed by cyclization. Cystine has been used to obtain cyclic analogues of Org 2766 viz. H-Cys-Glu-His-Cys-D-Lys-Phe-OH, H-Cys-Ala-Ala-Cys-D-Lys--Phe-OH and H-Cys-Ala-Ala-Phe-D-Lys-Cys-OH (patent application 0052028 of Roussel-UcIaf), and the peptides were tested for activity in the pole-jumping test. Unfortunately, one cannot conclude from their data if cyclization has resulted in an increase or decrease in activity since no reference peptide has been included to compare potencies. In the literature cyclization of [Lys ]ACTH--(5-10) (the COOH group of Gly with the 6-NH2 function of Lys ) has been reported the resulting peptide was inactive in steroidogenesis (61). Increase of the ring size with three atoms (a Gly residue), however, resulted in a peptide that was more active... 

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