The role of a second-shell residue in modifying substrate and inhibitor interactions in the SHV [beta]-lactamase: a study of ambler position Asn276

Mutagenesis studies were performed to better understand the basis of the inhibitor-resistant phenotype in SHV A [beta]-lactamase and also examine the role of a second-shell residue, Asn276. The results confirmed residue 276 as an important second-shell residue in class A [beta]-lactamase-mediated resistance to substrates and inhibitors, and also revealed Asn ablility to precisely modulate the conformational flexibility of Arg244 required for successful evolution in nature.