Jcm. Uitdehaag et al., Enzymatic circularization of a malto-octaose linear chain studied by stochastic reaction path calculations on cyclodextrin glycosyltransferase, PROTEINS, 43(3), 2001, pp. 327-335
Cyclodextrin glycosyltransferase (CGTase) is an enzyme belonging to the ol-
amylase family that forms cyclodextrins (circularly linked oligosaccharides
) from starch. X-ray work has indicated that this cyclization reaction of C
GTase involves a 23-Angstrom movement of the nonreducing end of a linear ma
lto-oligosaccharide from a remote binding position into the enzyme acceptor
site. We have studied the dynamics of this sugar chain circularization thr
ough reaction path calculations. We used the new method of the stochastic p
ath, which is based on path integral theory, to compute an approximate mole
cular dynamics trajectory of the large (75-kDa) CGTase from Bacillus circul
ans strain 251 on a millisecond time scale. The result was checked for cons
istency with site-directed mutagenesis data. The combined data show how aro
matic residues and a hydrophobic cavity at the surface of CGTase actively c
atalyze the sugar chain movement, Therefore, by using approximate trajector
ies, reaction path calculations can give a unique insight into the dynamics
of complex enzyme reactions. (C) 2001 Wiley-Liss, Inc.