KDPG aldolase                         "Designing a better kind of catalyst"
  Enzymes are some of the most effective catalyst known to man.  Their catalytic efficiency is seen in the enhancement in reaction rate, their selectivity for the substrates as well as the stereospecificity for the product.  This coupled with their environmentally friendly nature, enzymes have the potential to be attractive alternatives to standard organic catalysts.  Unfortunately, proteins are limited by their instability in industrial environments and narrow substrate tolerance.  Furthermore, controlled alterations of a protein scaffold was not possible so systematic methods to design protein were not possible. Only recently have advances in molecular biology, recombinant gene technologies, and crystallography have created the opportunity for true protein engineering.  To this end, many 

 

Crystal structure of E. coli KDPG Aldolase


Wymer N, Buchanan LV, Henderson D, Metha N, Botting CH, Procivavsek L, Fierke CA, Toone EJ, and Naismith JH.  Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli. (2001) Structure.  9,  1-20

investigators aspire to develop better protein based catalysts for academic and industrial applications.

    We are interested in KDPG aldolase, a bacterial enzyme that catalyzes the aldol cleavage of 2-keto-3-deoxy-6-phosphogluconate into pyruvate and glyceraldehyde- 3-phosphate.  The aldolase project is an effort to develop enzymes with altered substrate specificities such that they are capable of performing aldol additions between unnatural substrates.  We are currently employing two methods to achieve our goal, directed evolution and structure-based redesign.   

Recent Publications     

  1. Griffiths JS, Wymer N, Njolito E, Niranjanakumari S, Fierke CA, Toone EJ. Cloning, isolation and characterization of the Thermotoga maritima KDPG aldolase.
    (2002) Bioorg Med Chem. 10, 545-50.
  2. Wymer N, Buchanan LV, Henderson D, Mehta N, Botting CH, Pocivavsek L, Fierke CA, Toone EJ, Naismith JH.  Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli. (2001) Structure.  9, 1-9.

PubMed Search

Collaborators
Eric J Toone, Duke University, NC
James Naismith, University of St Andrews, UK
Heather A Carlson, University of Michigan, MI 

Project Researchers
Graduate Students
Manoj Cheriyan
Lance W. Rider

Questions about this project? Email Manoj at mcheriya@umich.edu

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