Liver conformational changes

W. R. Laws and J. D. Shore, Spectral evidence for tyrosine ionization linked to a conformational change in liver alcohol dehydrogenase ternary complexes, J. Biol. Chem. 254, 2582-2584 (1979). 

Glucose binding to an allosteric site of the phosphorylase a isozyme of liver induces a conformational change that exposes its phosphory-lated Ser residues to the action of phosphorylase a phosphatase 1 (PP1). 

The crystalline liver FDPase preparations show little activity at neutral pH, which suggests that the enzyme in situ may exist in a modified, activated form (see above). It has been suggested that the required conformational change can be induced by modification of a limited number of the 20 sulfhydryl groups in the protein (44) ... 

Alcohol oxidation requires release of a proton, which formally comes from the alcohol. In other dehydrogenases such as lactate dehydrogenase, proton release occurs simultaneously with hydride transfer. In liver ADH proton release can be demonstrated, by reaction of the proton with an indicator such as thymol blue or phenol red in stopped-flow spectrophotometry, to be faster than hydride transfer, 270 vs. 150 s and unaffected by use of deuterated substrate, so it occurs before hydride transfer. Binding of the NAD+ nicotinamide ring is accompanied by a conformational change of ADH bringing the catalytic zinc about 0.1 nm closer to the... 

The addition of 1 x 10 3 M acetyl glutamate to frog liver enzyme preparation causes a 10% and immediate increase in fluorescence. This effect has been confirmed by Edelhoch (8), who concurs in our interpretation that this finding signifies acetyl glutamate-induced conformational changes of carbamyl-P synthetase. We believe that the decrease in stability induced by substrates and cofactors is, whenever it is found to occur, the simplest and most sensitive method available for the detection and study of conformational changes in enzymic proteins. 

Branden, C.-l., Ekiund, H. Coenzyme-induc conformational changes and substrate binding in liver alcohol dehydrogenase in Molecular Interactions and Activity in Proteins, Ciba Foundation Symp. 60 (New Kries), pp. 63-80, Ezceipta M Uca, Amsterdam, 1978... 

Tapia and Eklund (1986) carried out a Monte Carlo simulation of the substrate channel of liver alcohol dehydrogenase, based on the X-ray diffraction structure for this enzyme. The addition of substrate and the associated conformation change induce an order—disorder transition for the solvent in the channel. A solvent network, connecting the active-site zinc ion and the protein surface, may provide the basis for a proton relay system. A molecular dynamics simulation of carbonic anhydrase showed two proton relay networks connecting the active-site zinc atom to the surrounding solvent (Vedani et ai, 1989). They remain intact when the substrate, HCOf, is bound. 

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