Computational Chemical Analysis of Firefly Luciferase Catalyzed Enantioselective Thioester Formation toward Ketoprofen

Kazuhiro SASAa*, Dai-Ichiro KATOb, Takeshi UNOc, Haruhisa HAYASHId and Hidehiko NAKANOb

aFukui National College of Technology
Geshi, Sabae, Fukui 916-8507, JAPAN
bDepartment of Materials Science and Chemistry, Graduate School of Engineering, University of Hyogo
2167 Shosha, Himeji, Hyogo 671-2280, JAPAN
cDepartment of Management and Information Sciences, Hiroshima Prefectural University
562 Nanatuka, Shobara, Hiroshima 727-0023, JAPAN
dLibrary and Academic Information Center, University of Hyogo
2167 Shosha, Himeji, Hyogo 671-2280, JAPAN

(Received: August 7, 2008; Accepted for publication: December 4, 2008)

Firefly luciferase is a well-known enzyme that participates in the bioluminescence reaction. Recently, it was reported that this enzyme also exhibits enantioselective thioester formation activity of 2-arylpropanoic acid such as ketoprofen. However, the enantiodifferential mechanism was still unknown. Therefore to clarify the reason of enantioselective thioester formation toward ketoprofen, we have performed molecular dynamics (MD) simulations for three kinds of firefly luciferase / acyl-AMP intermediate analogue complexes. Targeted substrates were N-acylsulfamate derivatives of R-ketoprofen, S-ketoprofen and 3-benzoylphenylacetic acids. Our results show that the dynamic behavior of Ser200 and Ser201 around the asymmetric carbon atom in the complexes is quite different.

Keywords: Firefly luciferase, Ketoprofen, Thioesterification, Enantioselectivity, Molecular dynamics

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