Alcohol dehydrogenase binding

Cedergren-Zeppezauer, E., Samama, J. P., Eklund, H. (1982) Crystal structure determinations of coenzyme analogue and substrate complexes of liver alcohol dehydrogenase binding... 

Cedergren-Zeppezauer E, Samama J-P, Eklund H (1982) Crystal structure determinations of coenzyme analogue and substrate complexes of liver alcohol dehydrogenase Binding of 1,4,5,6-tetrahydronicotin-amide adenine dinucleotide and trans-4-(N,N-dimethylamino)cinnam-aldehyde to the enzyme. Biochemistry 21 4895-4908 Cherest M, Felkin H, Prudent N (1968) Tortional strain involving partial bonds. The stereochemistry of the lithium aluminium hydride reduction of some simple open-chain ketones. Tetrahedron Lett 2199-2204... 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

The crystal structure of the HNL isolated from S. bicolor (SbHNL) was determined in a complex with the inhibitor benzoic acid." The folding pattern of SbHNL is similar to that of wheat serine carboxypeptidase (CP-WII)" and alcohol dehydrogenase." A unique two-amino acid deletion in SbHNL, however, is forcing the putative active site residues away from the hydrolase binding site toward a small hydrophobic cleft, thereby defining a completely different active site architecture where the triad of a carboxypeptidase is missing. 

Zn -containing alcohol dehydrogenase Linum usitatassimum HNL (L//HNL) has an ADP-binding /3a[3 domain and catalytic domain containing two Zn2+, which are not directly involved in catalysis [17]. 

Santhoshkumar, P., and Sharma, K.K. (2002) Identification of a region in alcohol dehydrogenase that binds to ot-crystallin during chaperone action. Biochim. Biopbys. Acta 1589, 115-121. 

The most extensively studied alcohol dehydrogenases are those of mammalian liver. They are dimeric proteins, with each subunit binding two Zn2+ ions, only one of which is catalytically active. This catalytic Zn2+ ion has distorted tetrahedral geometry, coordinated to one histidine and two cysteine residues. The non-catalytic zinc plays a structural role and is coordinated tetrahedrally to four cysteine residues. 

Thus, the role of zinc in the dehydrogenation reaction is to promote deprotonation of the alcohol, thereby enhancing hydride transfer from the zinc alkoxide intermediate. Conversely, in the reverse hydrogenation reaction, its role is to enhance the electrophilicity of the carbonyl carbon atom. Alcohol dehydrogenases are exquisitely stereo specific and by binding their substrate via a three-point attachment site (Figure 12.7), they can distinguish between the two-methylene protons of the prochiral ethanol molecule. 

Chin, J.K. and Klinman, J.P. (2000). Probes of a role for remote binding interactions on hydrogen tunneling in the horse liver alcohol dehydrogenase reaction. Biochemistry 39, 1278-1284... 

Alberty analyzed the anion effect on pH-rate data. He first considered a one-substrate, one-product enzyme-catalyzed reaction in which all binding interactions were rapid equilibrium phenomena. He obtained rate expressions for effects on F ax and thereby demonstrating how an anion might alter a pH-rate profile. He also considered how anions may act as competitive inhibitors. The effect of anions on alcohol dehydrogenase has also been investigated. Chloride ions appear to affect the on- and off-rate constants for NAD and NADH binding. See also pH Studies Activation Optimum pH... 

A sequential enzyme-catalyzed reaction mechanism in which two substrates react to form two products and in which there is a preferred order in the binding of substrates and release of products. Several enzymes have been reported to have this type of binding mechanism, including alcohol dehydrogenase , carbamate kinase , lactate dehydrogenase , and ribitol dehydrogenase. ... 

An enzyme reaction mechanism involving A binding before B and followed with the random release of products. In the absence of products and abortive complexes, the steady-state rate expression is identical to the rate expression for the ordered Bi Bi mechanism . A random on-ordered off Bi Bi mechanism has been proposed for a mutant form of alcohol dehydrogenase. ... 

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