TCBG Seminar

Michaelis Complex Formation in Enzymes that Hydrolyse Carbohydrate Polymers: Steered MD through Mapping into an Alternate Coordinate Space

Dr. Aaron Oakley
Australian National University
Canberra, Australia

Tuesday, November 28, 2006
2:00 pm (CT)
5602 Beckman Institute


The most abundant biopolymers in nature are carbohydrates. These are mainly polymers of pyranoses such as beta-D-glucose. The hydrolysis of polymers of pyranoses by enzymes begins with the formation of a Michaelis complex in which the sugar ring adjacent to the scissile bond is distorted away from its ground state "chair" conformation toward a "skew" form. This enables the formation of a transition state in which the sugar ring has significant oxocarbenium character. The type of skew forms taken is both enzyme and substrate dependent. Using the coordinate space for 6-membered rings defined by Pickett and Strauss, I use molecular dynamics to steer the pyranose ring away from chair to skew form in a maner which avoids biasing the type of skew form that results. This method reproduces observed skew conformations observed by crystallography and may be a powerful predictive tool for determining conformational itineraries of sugar rings in glycoside hydrolyses generally.

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