title: Crystal structure of L-2-haloacid dehalogenase from Pseudomonas sp. YL. An alpha/beta hydrolase structure that is different from the alpha/beta hydrolase fold.
abstract: L-2-Haloacid dehalogenase catalyzes the hydrolytic dehalogenation of L-2-haloalkanoic acids to yield the corresponding D-2-hydroxyalkanoic acids. The crystal structure of the homodimeric enzyme from Pseudomonas sp. YL has been determined by a multiple isomorphous replacement method and refined at 2.5 A resolution to a crystallographic R-factor of 19.5%. The subunit consists of two structurally distinct domains: the core domain and the subdomain. The core domain has an alpha/beta structure formed by a six-stranded parallel beta-sheet flanked by five alpha-helices. The subdomain inserted into the core domain has a four helix bundle structure providing the greater part of the interface for dimer formation. There is an active site cavity between the domains. An experimentally identified nucleophilic residue, Asp-10, is located on a loop following the amino-terminal beta-strand in the core domain, and other functional residues, Thr-14, Arg-41, Ser-118, Lys-151, Tyr-157, Ser-175, Asn-177, and Asp-180, detected by a site-directed mutagenesis experiment, are arranged around the nucleophile in the active site. Although the enzyme is an alpha/beta-type hydrolase, it does not belong to the alpha/beta hydrolase fold family, from the viewpoint of the topological feature and the position of the nucleophile.
authors.affiliation: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hisano
authors.forename: Y
authors.initials: Y
authors.lastname: Hata
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: J Q
authors.initials: JQ
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Kurihara
authors.forename: N
authors.initials: N
authors.lastname: Esaki
authors.forename: K
authors.initials: K
authors.lastname: Soda
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002264:Carboxylic Acids / Q000378:metabolism; D006846:Hydrocarbons, Halogenated / Q000378:metabolism; D006860:Hydrogen Bonding; D006867:Hydrolases / Q000648:ultrastructure*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011549:Pseudomonas / Q000201:enzymology*; D014961:X-Ray Diffraction
chemical_list: D002264:Carboxylic Acids; D006846:Hydrocarbons, Halogenated; D006867:Hydrolases; C034507:2-haloacid dehalogenase