CYP2E1 substrate inhibition. MECHANISTIC INTERPRETATION THROUGH AN EFFECTOR SITE FOR MONOCYCLIC COMPOUNDS.

VOLUME 283 (2008) PAGES 3487–3496

The “Experimental Procedures” and “Results” sections contained errors in nomenclature and in references to specific models and schemes, respectively.

PAGE 3489:

The following sentence, “Similar to the traditional mechanism for competitive inhibition, the inhibitor could bind only to free enzyme at the catalytic site to yield single-site inhibition,” should include a reference to model 1 of Scheme 2.

The following sentence, “Both substrate and inhibitor could alter binding of the other molecule (model 1),” should reference model 2a of Scheme 2 instead of model 1.

The following sentence, “For model 2, only substrate acted allosterically, such that substrate affected inhibitor binding (K_i ≠ K_si) but inhibitor did not affect substrate binding (K_s = K_is),” should reference model 2b of Scheme 2 instead of model 2.

The following sentence, “Model 3 described the alternative possibility wherein inhibitor was the only allosteric effector,” should reference model 2c of Scheme 2 instead of model 3.

The following sentence, “In the absence of allosterism (traditional noncompetitive inhibition, model 4), all inhibition constants were the same and the ESI and EIS complexes were equivalent,” should reference model 2d of Scheme 2 instead of model 4.

PAGE 3490:

The following sentence, “CYP2E1 demonstrated a relatively low K_ss (24 μm) and the rapid turnover of 47 min⁻¹ for pNP; nevertheless, at higher pNP concentrations (>100 μm), the activity gradually decreased as a second molecule bound to CYP2E1 through an effector site (K_s 260 μm), which inhibited activity at the catalytic site (Table 3),” was incorrect. It should read as follows. “CYP2E1 demonstrated a relatively low K_m (24 μm) and the rapid turnover of 47 min⁻¹ for pNP; nevertheless, at higher pNP concentrations (>100 μm), the activity gradually decreased as a second molecule bound to CYP2E1 through an effector site (K_ss 260 μm), which inhibited activity at the catalytic site (Table 3).”

These corrections do not change the interpretation of the results or conclusions of this article.