Dehalogenases

Figure C2.7.8. Catalytic cycle indicating the working of tire enzyme haloalkane dehalogenase [11],...

Verschueren K H G, Seljee F, Rozeboom J, Kalk K H and Dijkstra B W 1993 Crystallographic analysis of the catalytic mechanism of haloalkane dehalogenase Nature 363 693-8... 

Nucleophilic substitution is one of a variety of mechanisms by which living systems detoxify halogenated organic compounds introduced into the environment Enzymes that catalyze these reactions are known as haloalkane dehalogenases The hydrolysis of 1 2 dichloroethane to 2 chloroethanol for example is a biological nude ophilic substitution catalyzed by a dehalogenase... 

Scheme 10.32 Examples of reactions catalyzed by different classes of dehalogenases. HD haloalcohol dehalogenase EH epoxide hydrolase CL p-chlorobenzoyl-CoA ligase CBD p-chlorobenzoyl-CoA dehalogenase.

Scheme 10.33 Schematic representation of the mechanism of SDRs (top) and the halohydrin dehalogenase HheC (bottom). Scheme adapted from Reference 129.

The crystal structure of the halohydrin dehalogenase from the soil bacterium Agrobacterium radiobacter ADI, HheC, has been solved [129]. HheC is structurally related to the family of NAD(P)H-dependent short-chain dehydrogenases/reduc-... 

The reversibility of halohydrin dehalogenase-catalyzed reactions has been used for the regioselective epoxide-opening with nonnatural nucleophiles (an example is given in Scheme 10.34) [133]. The stereoselectivity of the enzyme results in the resolution of the racemic substrate. At the same time, the regioselectivity imposed by the active site geometry yields the anti-Markovnikov product. [128]... 

This is an emerging field that has not reached its final position yet. Members of the novel class of FCP, SCP, and HAD phosphatases require Mg2+ for catalysis. An aspartate residue within the active site signature motif (DxDx(T/V)) is essential to form an acyl-phosphate intermediate. Many members of the the HAD (haloacid dehalogenase) superfamily have phosphoesterase activity [3]. Some of those protein phosphatases act on... 

Figure 6.74 Ring-opening reactions catalyzed by halohydrin dehalogenase.

Ring opening of epoxides with nucleophiles other than water (Cl, BrT I, NOz , CN ) can also be catalyzed by halohydrin dehalogenase enzymes (EC 3.8.1.5, also named haloalkane dehalogenase or haloalcohd dehalogenase) (Figure 6.74) [197]. 

Specific Activity (pmol Bromide Produced per mg Protein per min) of Dehalogenase from Selected Species of Mycobacteria toward 1,2-dibromoethane... 

Jesenska A, M Bartos, V Czernekova, I Rychh k, I Pavlik, J Damborsky (2002) Cloning and expression of the haloalkane dehalogenase gene dhmA from Mycobacterium avium N85 and preliminary characterization of DhmA. Appl Environ Microbiol 68 3224-3230. 

Magnuson JK, ME Romine, DR Burris, MT Kingsley (2000) Trichlorethene reductive dehalogenase from Dehalococcoides ethenogenes. squence of tceA and substrate characterization. Appl Environ Microbiol 66 5141-5147. 

Chang KH, P-H Liang, W Beck, JD Scholten, D Dunaway-Mariano (1992) Isolation and characterization of the three polypeptide components of 4-chlorobenzoate dehalogenase from Pseudomonas sp. strain CBS-3. Biochemistry 31 5605-5610. 

Thomas AW, J Lewington, S Hope, AW Topping, AJ Weightman, JH Slater (1992) Environmentally directed mutations in the dehalogenase system of Pseudomonas putida strain PP3. Arch Microbiol 158 176-182. 

Marches JR, AJ Weightman (2003) Comparing the dehalogenase gene pool in cultivated a-halocarboxylic aciddegrading bacteria with the environmental matagene pool. Appl Environ Microbiol 69 4375-4382. 

Li Y-F, Y Hata, T Fujii, T Hisano, M Nishihara, T Kurihara, N Esaki (1998) Crystal structures of reaction intermediates of L-2-haloacid dehalogenase and implications for the reaction mechanism. J Biol Chem 273 15035-15044. 

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