Dehydratase large subunit. This family contains the large (alpha) subunit of B12-dependent glycerol dehydratases (GDHs) and B12-dependent diol dehydratases (DDHs). GDH is isofunctional with DDH. These enzymes can each catalyze the conversion of 1,2-propanediol, glycerol, and 1,2-ethanediol to the corresponding aldehydes via a coenzyme B12 (adenosylcobalamin)-dependent radical mechanism. Both enzymes exhibit a subunit composition of alpha2beta2gamma2. The enzymes differ in substrate specificity; glycerol is the preferred substrate for GDH and 1,2-propanediol for DDH. GDH shows almost equal affinity for both (R) and (S)-isomers while DDH prefers the (S) isomer. GDH plays a key role in the dihydroxyacetone (DHA) pathway and DDH in the anaerobic degradation of 1,2-diols. The radical mechanism has been well studied for Klebsiella oxytoca DDH and involves binding of 1,2-propanediol to the enzyme to induce hemolytic cleavage of the Co-C5' bond of the coenzyme to form cob(II)alamin and the adenosyl radical. Hydrogen abstraction from the substrate follows producing a substrate generated radical and 5'-deoxyadenosine. Rearrangement to the product radical is then followed by abstraction of a hydrogen atom from 5'-deoxyadenosine to produce the hydrated propionaldehyde and regenerate the adenosyl radical. After the Co-C5' bond is reformed and the hydrated aldehyde dehydrated, the process is complete. GDH has a higher affinity for coenzyme B12 than DDH. Both GDH and DDH are activated by various monovalent cations with K+, NH4+, and Rb+ being the most effective. However, DDH differs from GDH in that it is partially active with Cs+ and Na+. In general, the alpha and beta subunits for both enzymes are on different chains. However, for a subset of the GDHs, alpha and beta subunits appear to be on a single chain.
Structure:1IWP_AB; Klebsiella pneumoniae Glycerol dehydratase binds 1,2-propanediol, an essential catalytic K+ ion, and cobalamin; defined at 3.5A contacts.
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