Complex of Burkholderia cepacia lipase with transition state analogue of 1-phenoxy-2-acetoxybutane: biocatalytic, structural and modelling study.
In a series of four racemic phenoxyalkyl-alkyl carbinols, 1-phenoxy-2-hydroxybutane (1) is enantioselectively acetylated by Burkholderia cepacia (formerly Pseudomonas cepacia) lipase with an E value > or = 200, whereas for the other three racemates E was found to be < or = 4. To explain the high preference of B. cepacia lipase for (R)-(+)-1, a precursor of its transition state analogue with a tetrahedral P-atom, (R(P),S(P))-O-(2R)-(1-phenoxybut-2-yl)methylphosphonic acid chloride was prepared and crystallized in complex with B. cepacia lipase. The X-ray structure of the complex was determined, allowing to compare the conformation of the inhibitor with results of molecular modelling.
Luić
M
M
Rudjer Boskovic Institute, Zagreb, Croatia] Institut für Chemie-Kristallographie, Freie Universität Berlin, Germany. luic@faust.irb.hr
Tomić
S
S
Lescić
I
I
Ljubović
E
E
Sepac
D
D
Sunjić
V
V
Vitale
L
L
Saenger
W
W
Kojic-Prodić
B
B
D016956:Burkholderia cepacia / Q000201:enzymology*; D002384:Catalysis; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008049:Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009943:Organophosphorus Compounds / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
C432663:O-(1-phenoxybut-2-yl)methyl phosphonic acid chloride; D009943:Organophosphorus Compounds; D008049:Lipase