Enzyme diol dehydratase

This property of alkylcobaloximes and alkylcobalamins has been used to model the conversion of 1,2-diols to aldehydes catalyzed by the adenosyl-cobalamin-dependent enzyme diol dehydratase. For example, both organo-cobalamins (726, 126a) and alkylcobaloximes 126a, b) were shown to convert 1,2-diols to aldehydes under photolytic conditions. Lappert et al. 

Schramm E, B Schink (1991) Ether-cleaving enzyme and diol dehydratase involved in anaerobic polyethylene glycol degradation by a new Acetobacterium sp. Biodegradation 2 71-79. 

The structure of the E. coli enzyme (Fig. 16-24) shows methylcobalamin bound in a base-off conformation, with histidine 759 of the protein replacing dimethylbenzimidazole in the distal coordination position on the cobalt. This histidine is part of a sequence Asp-X-His-X-X-Gly that is found not only in methionine synthase but also in methylmalonyl-CoA mutase, glutamate mutase, and 2-methyleneglutarate mutase. However, diol dehydratase lacks this sequence and binds adenosylcobalamin with the dimethylbenz-imidazole-cobalt bond intact.417... 

Tobimatsu, T., Sakai, T., Hashida, Y., Mizoguchi, N., Miyoshi, S., and Toraya, T., 1997, Heterologous expression, purification, and properties of diol dehydratase, an adenosylcobalamin-dependent enzyme of Klebsiella oxytoca, Arch. Biochem. Biophys. 347 1320140. 

About 10 coenzyme B -dependent enzymes are now known (reviewed in References 13,14, and 76 see Table 1) four carbon skeleton mutases (methylmalonyl-CoA mutase (MMCM), glutamate mutase (GM), methylene glu-tarate mutase (MGM), isobutyryl-CoA mutase (ICM) ), diol dehydratase (DD), glycerol dehydratase, ethanol-amine anunonia lyase (EAL), two amino mutases, and Bi2-dependent ribonucleotide reductase. The coenzyme Bi2-dependent enzymes are unevenly distributed in the living world, and MMCM is the only enzyme that is also indispensable in human metabolism. ... 

The enzyme-coenzyme partnership involving diol dehydratase catalyzes the dehydration of both ethane-1,2-diol and propane-1,2-diol. 

The first common step in AdoCbl-dependent readions is homolytic cleavage of the cobalt-carbon bond to generate a radical pair, cob(ii)alamin and the carbon-centered dAdo radical (Scheme 19.3). This reaction experiences a 10 -fold rate enhancement in B12 enzymes [14, 15] in the presence of substrate, and the mechanism for this rate acceleration has been the subject of extensive scrutiny. Thus, in methylmalonyl-CoA mutase and in glutamate mutase, little if any destabilization of the cobalt-carbon bond is observed in the reactant state, as revealed by resonance Raman spectroscopy [16, 17], and the intrinsic substrate binding is utilized to labilize the bond. In contrast, approximately half of the destabilization of the cobalt-carbon bond in diol dehydratase is expressed in the reactant state. This re-... 

Diol dehydratase and ethanolamine ammonia lyase exhibit the largest overall tritium isotope effects that have been measured in Bi2-dependent enzymes [44, 45], the overall deuterium kinetic isotope effect is also substantial [10, 34, 45]. The observation of a deuterium isotope effect on the pre-steady-state formation of cob(ii)alamin in diol dehyratase [10] and in ethanolamine ammonia lyase [25] is consistent with kinetic coupling between the homolysis and H-transfer steps. 

Shibata, N., Masuda, J., Tobimatsu, T., Toraya, T., Suto, K., Morimoto, Y., Yasuoka, N. (1999) A new mode of Bi2 binding and the direct participation of a potassium ion in enzyme catalysis X-ray structure of diol dehydratase, Structure Fold Des. 7, 997-1008. 

Diol dehydratase (DD) and glycerol dehydrates (GD) are isofunctional enzymes that catalyze the dehydration of glycerol, ethane-1,2-diol and propane-1,2-diol to 3-hydroxypropanal, acetaldehyde and propanal, respectively (other glycols can be dehydrated in an analogous fashion) [210] (see Fig. 19). DD has about a twofold preference for propane-1,2-diol to glycerol, whereas GD prefers glycerol to propane-1,2-diol as a substrate [178]. Conversion of glyc-... 

Dehydratases. There are two enzymes known (diol dehydratase and glycerol dehydratase) that catalyze the internal disproportionation of a 1,3-diol (or a vicinal triol) to a corresponding 1,1-diol, which dehydrates to an aldehyde. In all of these (see Table 2, entries 1 and 2), coenzyme B12 (AdoCbl, 2) acts as the cofactor, indicated to induce a sequence of steps with radical intermediates by the homolysis of its organometallic bond. The corrinoid is bound in a classic base-on form, as evidenced by ESR spectroscopic investigations and X-ray analysis (70,76,84) (Fig. 15). 

A further investigation of the photolysis products of 4,5-dihydroxypentyl-(pyridine)cobaloxime and of 5,6-dihydroxyhexyl(pyridine)cobaloxime shows that the initially generated radicals rearrange by intramolecular hydrogen shifts. Furthermore, the primary radicals, which attack the vicinal diols, do so regio-selectively and show considerable primary kinetic isotope effects. In all these features the system thus mimics aspects of the diol-dehydratase enzyme system. 

Y., Yasuoka, N., and Toraya, T. (2002) Substrate-induced conformational change of a coenzyme B12-dependent enzyme crystal structure of the substrate-free form of diol dehydratase. Biochemistry, 41 (42), 12607-12617. 

---