TABLE 4

Experimental and computational results of inhibition study with compound 6142342

EnzymeExperimental % inhibition with 40 μM inhibitoraComputational result
Binding energy (kcal/mol)bInhibitor-enzyme distance (Å)c
O-1–Zn1O-1–Zn2O-3–Zn1O-2–K224 N-ζN-3–K150a N-ζ
IMP-1-V67Ad33 ± 10−10.7 ± 0.52.31.92.12.93.4
IMP-1 (V67)85 ± 5−11.8 ± 0.82.11.92.03.13.2
IMP-1-V67I58 ± 11−11.4 ± 0.42.31.81.92.73.6
IMP-10 (F67)49 ± 5−11.0 ± 0.62.11.92.23.03.3
  • a Percent inhibition values are the averages for three experiments ± standard deviations.

  • b The binding energies reported are the average binding energies of the highest-ranked clusters of docking conformations ± standard deviations.

  • c The distances reported are distances between inhibitor atoms and enzyme atoms found in the highest-ranked docking conformation (see Fig. 4B). O-1 is the nitro group oxygen coordinating the two Zn(II) ions, O-2 is the nitro group oxygen hydrogen bonding with K224, O-3 is the deprotonated phenol oxygen coordinating Zn1, and N-3 is the benzothiazole nitrogen that interacts electrostatically with K150a.

  • d Amino acid identities are shown in bold.