Molecular Modeling Studies of the Conserved B12-Binding Motif and Its Variants from Clostridium tetanomorphum Glutamate Mutase

The coupling of an aspartate residue with an active site histidine plays a pivotal role in enzyme catalysis. The His-Asp pair in glutamate mutase and other B12-dependent mutases is not only responsible for coenzyme-binding, but is also involved in fine-tuning the enzymatic activities. Our modeling results show that the His-Asp pair is arranged in a highly organized manner. Except for carboxymethylated Cys or Glu, a less hindered or non-charged amino acid residue is preferred between the conserved histidine and aspartate residue.