Glutamate conformational analysis

N 017 "Conformational Analysis of Macromolecules. IV. Helical Structures of PolyfL-alanine), Poly(L-valine), Poly(p-methyl-L-aspartate), Polyly-methyl-l.-glutamate),... 

N 022 "Conformational Analysis of Macromolecules. V. Helical Structures of PolylL-aspartic acid) and PolylL-glutamic acid), and Related Compounds"... 

G., and Scheraga, H.A., 1967, Conformational analysis of macromolecules. IV. Helical structure of poly-L-alanine, poly-L-valine, poly- 3-methyl-L-aspar-tate, poly-Y -methyl-L-glutamate, and poly-L-tyrosine, J. 

On the other hand, the dispersions obtained by Yang and Doty (1957) for poly-y-benzyl-L-glutamate in a mixture of /3-forms and coil forms did not obey the simple Drude equation, and Imahori s analysis of these data yielded positive Moffitt slopes and intercepts after corrections had been made for the intrinsic residue contribution (Imahori, 1960). Imahori has moreover found that denatured bovine serum albumin and ovalbumin in solution display positive ba and corrected ao values in sharp contrast to the negative slopes characteristic of the native proteins and has in addition been able to correlate the positive slopes with the /3-form in the protein precipitates by infrared spectra. Wada et al. (1961) have recently carried forward this suggestion that the (8-conformation displays complex disper-... 

What accommodations, then, must be made in the pattern of analysis developed for standard synthetic polypeptides if it is to yield quantitative estimates of partial helical content in proteins The requirements are much the same as those set out for poly-L-lysine (see Section III, G, 3), yet since globular proteins, like copolymers of L-lysine and L-glutamic acid, cannot be made completely helical in aqueous solution, a helical reference conformation must be taken either from other standard molecules or from the nonaqueous behavior of the protein in question. This latter procedure involves solvent changes with little bearing on native conditions and may be impossible to carry out in the face of restraints imposed by proline and cross-links, so that standard helical dispersion can more feasibly serve as this reference conformation. 

A value of be = —630 is well established for synthetic polypeptides and fibrous proteins. The considerations leading to the reasonable approximation that be of the disordered chain is zero, together with the implied equality of Xo and for this state, have been discussed in Section III, C, 1, and incorporated into the pattern of analysis for partial helical content as set out in Section III, G, 2. A value of ao = 4-650 has been obtained for poly-L-glutamic acid, poly-L-lysine, and Pinna nobilis tropomyosin under the appropriate conditions. As has been stressed, these constants have conformational significance only when a value of 212 nm is used for Xo. 

Analysis of the TBPA-Ti complex (39,40) indicates that the binding site for the hormone is located deep inside the channel. The hormone makes extensive interactions with the protein side chains that project into the channel. The 4 -hydroxyl of Ti interacts with a patch of hydroxy-amino acids of the protein while each of the iodines makes contact with a number of hydro-phobic protein residues. The T amino acid side chain functional groups are in appropriate positions to interact with glutamic acid and lysine residues. Thus, this channel provides a favorable environment for each of the characteristic substituents of the thyroid hormone (40). However, because of the Ti orientation disorder in the protein complex, this structural model is not a sensitive measure of the observed correlations between diphenyl ether conformations and binding affinity data. 

Costantino, G., Macchiarulo, A., Pellicciari, R 1999, Pharmacophore models of group 1 and group 11 metabotropic glutamate receptor agonists. Analysis of conformational, steric, and topological parameters affecting potency and selectivity. J, Med. Chem, 42, 2816-2827. 

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