Structural Basis for Substrate Specificity in Adenosylcobalamin-dependent Isobutyryl-CoA Mutase and Related Acyl-CoA Mutases

Background: Acyl-CoA mutases catalyze radical-based carbon skeleton rearrangements. Results: Crystal structures of isobutyryl-CoA mutase in complex with four different substrates reveal active site architecture and determinants of substrate specificity. Conclusion: Identification of specificity-determining residues allows for prediction of new acyl-CoA mutase activities. Significance: Improved understanding of acyl-CoA mutase substrate specificity is critical for biotechnological and engineering applications.