Enzymatic circularization of a malto-octaose linear chain studied by stochastic reaction path calculations on cyclodextrin glycosyltransferase

Citation
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
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
43
Issue
3
Year of publication
2001
Pages
327 - 335
Database
ISI
SICI code
0887-3585(20010515)43:3<327:ECOAML>2.0.ZU;2-6
Abstract
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.