Linear free energy relationships implicate three modes of binding for fluoroaromatic inhibitors to a mutant of carbonic anhydrase II

Linear free energy relationships between binding affinity and hydrophobicit y for a library of fluoroaromatic inhibitors of F131V carbonic anhydrase II (CA) implicate three modes of interaction. X-ray crystal structures sugges t that F131 interacts with fluoroaromatic inhibitors, while P202, on the op posite side of the active site cleft, serves as the site of the hydrophobic contact in the case of the F131V mutant. 2-Fluorinated compounds bind more tightly, perhaps due to the field effect of the nearby fluorine on the aci dity of the amide proton.