Binding modes of DL-2-haloacid dehalogenase revealed by crystallography, modeling and isotope effects studies.
Several pathways of biotic dechlorination can be found in enzymes, each characterized by different chlorine isotopic fractionation, which can thus serve as a signature of a particular mechanism. Unlike other dehalogenases, DL-2-haloacid dehalogenase, DL-DEX, converts both enantiomers of the substrate. Chlorine isotope effects for this enzyme are larger than in the case of other dehalogenases. Recently, the 3D structure of this enzyme became available and enabled us to model these isotope effects and seek their origin. We show that the elevated values of the chlorine kinetic isotope effects originate in part in the processes of binding and migration within the enzyme active site that precede the dehalogenation step.
Faculty of Pharmacy, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland; Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
Agata
A
Siwek
Rie
R
Omi
Ken
K
Hirotsu
Keiji
K
Jitsumori
Nobuyoshi
N
Esaki
Tatsuo
T
Kurihara
Piotr
P
Paneth
D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007554:Isotopes; D062105:Molecular Docking Simulation; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011422:Propionates / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D007554:Isotopes; D011422:Propionates; D006867:Hydrolases; C034507:2-haloacid dehalogenase
Binding isotope effect; Chlorine isotope effect; DL-DEX; Dehalogenation; Mechanism