Cobalamin-dependent methionine synthase conformation is governed by the ligand trans effect

BIOL 200

Angela S. Fleischhacker, afleisch@umich.edu and Rowena G. Matthews, rmatthew@umich.edu. Life Sciences Institute and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109
Cobalamin-dependent methionine synthase (MetH) undergoes large conformational changes as it uses the cobalamin cofactor as a donor or acceptor in three separate methyl transfer reactions. The “base-off” form has been associated with a conformation of MetH that is poised for reactivation of the cofactor by reductive methylation rather than catalysis. Our studies on a variety of cob(III)alamins bound to MetH show a correlation between the accessibility of this conformation and the equilibrium between the 5- and 6-coordinate forms of the free cofactor in the order of the established trans effect. The trans effect also controls the affinity of MetH in the cob(III)alamin form for flavodoxin. Flavodoxin binds less tightly to MetH when the cob(III)alamin has a strong trans ligand and less positive charge on cobalt. Thus, access to the reactivation conformation is governed by the trans effect in cob(III)alamins and the net charge on the cobalt.
 

Enzymes
4:30 PM-6:30 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006