1PX0

Crystal structure of the haloalcohol dehalogenase HheC complexed with the haloalcohol mimic (R)-1-para-nitro-phenyl-2-azido-ethanol

Summary for 1PX0

• Entry DOI: 10.2210/pdb1px0/pdb
• Related: 1PWX 1PWZ
• Descriptor: halohydrin dehalogenase, (R)-1-PARA-NITRO-PHENYL-2-AZIDO-ETHANOL (3 entities in total)
• Functional Keywords: haloalcohol dehalogenase, halohydrin dehalogenase, halohydrin hydrogen-halide lyase, sdr family, short-chain dehydrogenase/reductase, rossmann fold, lyase
• Biological source: Agrobacterium tumefaciens
• Total number of polymer chains: 4
• Total formula weight: 112751.36

Authors

de Jong, R.M.,Tiesinga, J.J.W.,Rozeboom, H.J.,Kalk, K.H.,Tang, L.,Janssen, D.B.,Dijkstra, B.W. (deposition date: 2003-07-02, release date: 2003-10-07, Last modification date: 2023-08-16)

Primary citation

de Jong, R.M.,Tiesinga, J.J.W.,Rozeboom, H.J.,Kalk, K.H.,Tang, L.,Janssen, D.B.,Dijkstra, B.W.
Structure and Mechanism of a Bacterial Haloalcohol Dehalogenase: a new variation of the short-chain dehydrogenase/reductase fold without an NAD(P)H binding site
EMBO J., 22:4933-4944, 2003

PubMed Abstract: Haloalcohol dehalogenases are bacterial enzymes that catalyze the cofactor-independent dehalogenation of vicinal haloalcohols such as the genotoxic environmental pollutant 1,3-dichloro-2-propanol, thereby producing an epoxide, a chloride ion and a proton. Here we present X-ray structures of the haloalcohol dehalogenase HheC from Agrobacterium radiobacter AD1, and complexes of the enzyme with an epoxide product and chloride ion, and with a bound haloalcohol substrate mimic. These structures support a catalytic mechanism in which Tyr145 of a Ser-Tyr-Arg catalytic triad deprotonates the haloalcohol hydroxyl function to generate an intramolecular nucleophile that substitutes the vicinal halogen. Haloalcohol dehalogenases are related to the widespread family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDR family), which use a similar Ser-Tyr-Lys/Arg catalytic triad to catalyze reductive or oxidative conversions of various secondary alcohols and ketones. Our results reveal the first structural details of an SDR-related enzyme that catalyzes a substitutive dehalogenation reaction rather than a redox reaction, in which a halide-binding site is found at the location of the NAD(P)H binding site. Structure-based sequence analysis reveals that the various haloalcohol dehalogenases have likely originated from at least two different NAD-binding SDR precursors.

PubMed: 14517233
DOI: 10.1093/emboj/cdg479

Experimental method

X-RAY DIFFRACTION (1.9 Å)