(ii) Brief Account of How Sulfonamide Inhibitors are Isoenzyme-Selective (Problem V)
The present study investigated how PTS can selectively inhibit CA-II, and not CA-I. The study used Pymol to analyse molecular …show more content…
This size difference is suggested to be a consequence of the isoenzymes having different amino acids in the binding pocket of the active site. Histidine-200, histidine-67, and valine-62 in the active site of CA-I appeared to be the main amino acids which could potentially sterically hinder PTS. Further investigations, revealed that histidine-200 of CA-I sterically clashes with PTS, and this may significantly decrease the binding affinity of PTS. Whereas, in the binding pocket of CA-II the residues asparagine-62, asparagine-67, and threonine-200 do not appear to sterically hinder PTS. Instead, the analysis found evidence of hydrogen bonding between PTS and threonine 199, and 200, which appears to coordinate PTS to zinc.
PTS was determined to be wide and rigid having a heterocyclic two ring structure (Figure 1). This structure is suggested to prevent PTS from contorting its shape to fit through the narrow binding pocket of CA-I. Whereas, the wider binding pocket of CA-II can accommodate the wide and rigid PTS, hence PTS can interact with the