STRUCTURAL DETERMINATION OF IRON CONTAINING PROTEIN BY MAD PHASING: DRUG DESIGN

Cornell University Ithaca, Ithaca NY

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Abstract

Cellulomonas fimi beta -1,4-glycanase Cex The catalytic domain from Cex (cex-cd) is in many ways a prototype for the retaining beta-1,4-glycanase enzymes, which are of fundamental importance in the cleavage of common beta -1,4-linkages in saccharides and of practical interest in the alternate energy source industry in treating common forms of biomass. In collaboration with Drs. Steve Withers, Tony Warren and colleagues at the University of British Columbia, we have been able to study the X-ray structures of cex-cd both alone and in complex with intermediates in the catalytic mechanism of the enzyme. This has led to new insights into the recognition by this protein of specific saccharide moeities. It also helped address the long-standing debate about the nature of the intermediate of this reaction: we provided strong evidence supporting the covalent intermediate model. We have also been able to identify specific contacts between the enzyme and the substrate that may assist in forming the tranition state of the reaction.