Leucine-isoleucine-valine binding protein

Sack JS, Saper MA, Quiocho FA. Periplasmic binding protein structure and function. Refined X-ray structures of the leucine/isoleucine/valine-binding protein and its complex with leucine. Journal of Molecular Biology 1989, 206, 171-191. 

Masuko, T., Kashiwagi, K., Kuno, T., Nguyen, N. D., Pahk, A. J., Fukuchi, J., Igarashi, K., and Williams, K. (1999). A regulatory domain (R1-R2) in the amino terminus of the N-methyl-D-aspartate receptor Effects of spermine, protons, and ffenprodil, and structural similarity to bacterial leucine/isoleucine/valine binding protein. Mol. Pharmacol. 55, 957-969. 

Salopek-Sondi, B., Vaughan, M. D., Skeels, M. C., et al. (2003) 19F NMR studies of the leucine-isoleucine-valine binding protein evidence that a closed conformation exists in solution. J. Biomol. Struct. Dyn., 21(2), 235-246. 

Olah, G.A., Trakhanov, S., Trewhella, J., Quiocho, F.A., 1993. Leucine/isoleucine/valine-binding protein contracts upon binding of ligand. J. Biol. Chem. 268, 16241-16247. 

Figure 3. The muscle calcium binding protein molecule has the general shape of a prolate ellipsoid of revolution (59). The shell, 2.7-A thick, contains those atoms, exclusive of hydrogen, that would be exposed to the solvent were there no surface indentations. The oblate ellipsoid hydrocarbon core consists of side chains of phenylalanine, leucine, isoleucine, and valine.

For the 1H/I5N experiment, uniformly labeled substance is obtainable at a reasonable cost, but uniform 13C labeled proteins are more expensive. However, in some cases selective labeling of the methyl groups in valine, leucine, or isoleucine residues of a protein proves sufficient for screening purposes (59). The employment of HSQC experiments to detect binding is especially well exemplified in the technique termed SAR by NMR (33). 

Leucine is an essential, branched-chain amino acid that does not compete with tryptophan for nuclear tryptophan receptor binding in vitro.196 However, the addition of L-leucine to unlabeled L-tryptophan caused significantly less inhibition of 3H-tryptophan binding in vitro to hepatic nuclei than did unlabeled L-tryptophan alone.186 Also, L-isoleucine and L-valine revealed binding effects similar to that with L-leucine. In regard to hepatic protein synthesis, L-leucine alone has no effect, yet when added with L-tryp-tophan, it inhibits the increase of protein synthesis due to L-tryptophan alone. The mechanisms by which L-leucine acts are not yet clear. It does not appear to be related to altered transport of L-tryptophan, as can occur with branched-chain amino acids. Although L-leucine does not stimulate hepatic protein synthesis, it has been reported to stimulate muscle protein synthesis.188 Whether this effect of L-leucine on muscle may influence the liver response is not clear. 

Compounds 296-299 inhibit acetohydroxy acid synthase (AHAS), formerly known as acetolactate synthase. Its activity is not present in animals, but it has been found in all plants where measurements have been attempted. Acetohydroxy acid synthase catalyses the first step in production of branched amino acids (leucine, valine and isoleucine) (Scheme 73), which are obviously needed for the protein synthesis and cell growth. The compounds 296-299 seem to bind within the substrate-access channel of the enzyme, thus blocking a-ketocarboxylate access to the active site. While these herbicides are undoubtedly highly successful, resistance developed due to mutations within AHAS is becoming a serious problem [274, 275]. 

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