Trypsinogen-trypsin transition: a molecular dynamics study of induced conformational change in the activation domain.
The trypsinogen to trypsin transition has been investigated by a stochastic boundary molecular dynamics simulation that included a major portion of the trypsin molecule and the surrounding solvent. Attention focused on the "activation domain", which crystallographic studies have shown to be ordered in trypsin and disordered in its zymogen, trypsinogen. The chain segments that form the activation domain were found to exhibit large fluctuations during the simulation of trypsin. To model a difference between trypsin and trypsinogen, the N-terminal residues Ile-16 and Val-17 were removed in the former and replaced by water molecules. As a result of the perturbation, a structural drift of 1-2 A occurred that is limited to the activation domain. Glycine residues are found to act as hinges for the displaced chain segments.
Brünger
A T
AT
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
Huber
R
R
Karplus
M
M
D000595:Amino Acid Sequence; D004789:Enzyme Activation; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D014357:Trypsin / Q000378:metabolism*; D014362:Trypsinogen / Q000378:metabolism*
D014362:Trypsinogen; D014357:Trypsin