The X-Ray Structure of the Haloalcohol Dehalogenase HheA from Arthrobacter sp. Strain AD2: Insight into Enantioselectivity and Halide Binding in the Haloalcohol Dehalogenase Family

• DOI: 10.1128/jb.01866-05
• Publication Date: 2006-05-17T19:00:28Z
• Authors: René M. de Jong; Kor H. Kalk; Lixia Tang; Dick B. Janssen; Bauke W. Dijkstra
• Keywords: Dehalogenase

Haloalcohol dehalogenases are bacterial enzymes that cleave the carbon-halogen bond in short aliphatic vicinal haloalcohols, like 1-chloro-2,3-propanediol, some of which recalcitrant environmental pollutants. They use a conserved Ser-Tyr-Arg catalytic triad to deprotonate haloalcohol oxygen, attacks halogen-bearing carbon atom, producing an epoxide and halide ion. Here, we present X-ray structure dehalogenase HheA(AD2) from Arthrobacter sp. strain AD2 at 2.0-A resolution. Comparison with previously reported 34% identical enantioselective HheC Agrobacterium radiobacter AD1 shows has similar quaternary tertiary but much more open substrate-binding pocket. Docking experiments reveal can bind both enantiomers substrate 1-p-nitrophenyl-2-chloroethanol productive way, explains low enantiopreference HheA(AD2). Other differences found halide-binding site, where side chain amino group Asn182 is position stabilize halogen atom or ion HheA(AD2), contrast HheC, water molecule taken over this role. These results broaden insight into structural determinants govern reactivity selectivity family.