1pwz
From Proteopedia
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Crystal structure of the haloalcohol dehalogenase HheC complexed with (R)-styrene oxide and chloride
Overview
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.
About this Structure
1PWZ is a Single protein structure of sequence from Agrobacterium tumefaciens with and as ligands. Full crystallographic information is available from OCA.
Reference
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., de Jong RM, Tiesinga JJ, Rozeboom HJ, Kalk KH, Tang L, Janssen DB, Dijkstra BW, EMBO J. 2003 Oct 1;22(19):4933-44. PMID:14517233
Page seeded by OCA on Thu Feb 21 14:33:28 2008
Categories: Agrobacterium tumefaciens | Single protein | Dijkstra, B W. | Janssen, D B. | Jong, R M.de. | Kalk, K H. | Rozeboom, H J. | Tang, L. | Tiesinga, J J.W. | CL | RSO | Haloalcohol dehalogenase | Halohydrin dehalogenase | Halohydrin hydrogen-halide lyase | Rossmann fold | Sdr family | Short-chain dehydrogenase/reductase
