ARYL BIS-SULFONAMIDES BIND TO THE ACTIVE SITE OF A HOMOTRIMERIC ISOPRENOID BIOSYNTHESIS ENZYME ISPF AND EXTRACT THE ESSENTIAL DIVALENT METAL CATION COFACTOR

摘要

Characterizing the mode of action of non-covalent inhibitors in multisubunit enzymes often presents a great challenge. Most of the conventional used techniques often fail because they do not reveal how the distribution of individual ligand-bound states changes with ligand concentration but instead describe an average property of the ensemble as a function of ligand concentration. Thus, mixed models comprising both competitive and noncompetitive binding are often used that proved very little insight into the mechanisms of ligand binding and recognition.