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Enzymatic circularization of a malto‐octaose linear chain studied by stochastic reaction path calculations on cyclodextrin glycosyltransferase
Author(s) -
Uitdehaag Joost C.M.,
van der Veen Bart A.,
Dijkhuizen Lubbert,
Elber Ron,
Dijkstra Bauke W.
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.1044
Subject(s) - bacillus circulans , chemistry , cyclodextrin , glycosyltransferase , oligosaccharide , molecular dynamics , stereochemistry , enzyme , computational chemistry , biochemistry
Cyclodextrin glycosyltransferase (CGTase) is an enzyme belonging to the α‐amylase family that forms cyclodextrins (circularly linked oligosaccharides) from starch. X‐ray work has indicated that this cyclization reaction of CGTase involves a 23‐Å movement of the nonreducing end of a linear malto‐oligosaccharide from a remote binding position into the enzyme acceptor site. We have studied the dynamics of this sugar chain circularization through reaction path calculations. We used the new method of the stochastic path, which is based on path integral theory, to compute an approximate molecular dynamics trajectory of the large (75‐kDa) CGTase from Bacillus circulans strain 251 on a millisecond time scale. The result was checked for consistency with site‐directed mutagenesis data. The combined data show how aromatic residues and a hydrophobic cavity at the surface of CGTase actively catalyze the sugar chain movement. Therefore, by using approximate trajectories, reaction path calculations can give a unique insight into the dynamics of complex enzyme reactions. Proteins 2001;43:327–335. © 2001 Wiley‐Liss, Inc.