Histidine residues alcohol dehydrogenase

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.)...

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

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. 

Alcohol dehydrogenases (ADH EC 1.1.1.1), for which several X-ray structures are available ", catalyze the biological oxidation of primary and secondary alcohols via the formal transfer of a hydride anion to the oxidized form of nicotinamide adenine dinucleotide (NAD ), coupled with the release of a proton. Liver alcohol dehydrogenase (LADH) consists of two similar subunits, each of which contains two zinc sites, but only one site within each subunit is catalytically active. The catalytic zinc is coordinated in a distorted tetrahedral manner to a histidine residue, two cysteine residues and a water molecule. The remaining zinc is coordinated tetrahedrally to four cysteine residues and plays only a structural role . 

The active site of alcohol dehydrogenase contains a zinc ion that is coordinated to the sulfur atoms of two cysteine residues and a nitrogen atom of histidine (Figure 16,11). This zinc ion polarizes the carbonyl group of the substrate to favor the transfer of a hydride from NADH. 

Figure 16.10 Active site of alcohol dehydrogenase. The active site contains a itne ion bound to two cysteine residues and one histidine residue. Notice that the zinc ion binds the acetaldehyde substrate through its oxygen atom, ipolarizing the substrate so that it more easily accepts a hydride from NADH. Only the nicotinamide ring of NADH is shown.

The active site of alcohol dehydrogenase contains two cysteine residues (Cys 48 and Cys 174) and a histidine residue (His 67), all of which are coordinated to a zinc ion (Figure 6.20a). After NAD+ binds to the active site, the substrate ethanol enters and binds to the Zn2+ as the alcoholate anion (Figure 6.20b). The electrostatic effect of Zn2+ stabilizes the transition state. As the intermediate... 

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