Volume 26, Issue 3, Pages e3 (March 2018)

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Volume 26, Issue 3, Pages 383-390.e3 (March 2018) "To Be or Not to Be" Protonated: Atomic Details of Human Carbonic Anhydrase-Clinical Drug Complexes by Neutron Crystallography and Simulation Andrey Kovalevsky, Mayank Aggarwal, Hector Velazquez, Matthew J. Cuneo, Matthew P. Blakeley, Kevin L. Weiss, Jeremy C. Smith, S. Zoë Fisher, Robert McKenna Structure Volume 26, Issue 3, Pages 383-390.e3 (March 2018) DOI: 10.1016/j.str.2018.01.006 Copyright © 2018 Terms and Conditions

Structure 2018 26, 383-390.e3DOI: (10.1016/j.str.2018.01.006) Copyright © 2018 Terms and Conditions

Figure 1 Chemical Diagrams of the CAIs Studied with Neutron Crystallography to Date Structure 2018 26, 383-390.e3DOI: (10.1016/j.str.2018.01.006) Copyright © 2018 Terms and Conditions

Figure 2 Superposition of Bound hCA II Clinical Drugs from the Five Available Neutron Structures Hydrophilic sub-site is colored pink, and the hydrophobic sub-site is colored green. Water molecules present in the hydrophilic sub-site as observed in the neutron structures are omitted for clarity. The drugs—AZM (pink carbons), MZM (yellow carbons), BZM (magenta carbons), DZM (cyan carbons), and EZM (green carbons)—are shown as sticks and color-coded. Structure 2018 26, 383-390.e3DOI: (10.1016/j.str.2018.01.006) Copyright © 2018 Terms and Conditions

Figure 3 BZM Binding to hCA II Active Site (A) Hydrogen-bonding interactions of BZM with the residues of hydrogenous, H/D exchanged hCA II. 2FO-FC neutron-scattering length density map is contoured at 1.5σ level. (B) Hydration water architecture in the hCA II-BZM active site. 2FO-FC neutron-scattering length density map is contoured at 2.0 σ level for BZM and 1.0 σ level for D2Os. Zn2+ is depicted as gray spheres in all figures. Hydrogen bonds are shown as blue dashed lines; closely positioned functional groups that do not make hydrogen bonds are shown as black dotted lines. Structure 2018 26, 383-390.e3DOI: (10.1016/j.str.2018.01.006) Copyright © 2018 Terms and Conditions

Figure 4 DZM Binding to hCA II Active Site (A) Hydrogen-bonding interactions of DZM with the residues of deuterated hCA II. 2FO-FC neutron-scattering length density map is contoured at 1.5 σ level. (B) Hydration water architecture in the hCA II-DZM active site. DZM hydration water chain spans D2O molecules W1–W4. 2FO-FC neutron-scattering length density map is contoured at 1.5 σ level. Structure 2018 26, 383-390.e3DOI: (10.1016/j.str.2018.01.006) Copyright © 2018 Terms and Conditions

Figure 5 EZM Binding to hCA II Active Site (A) Hydrogen-bonding interactions of EZM with the residues of deuterated hCA II. 2FO-FC neutron-scattering length density map is contoured at 1.5 σ level. (B) Hydration water architecture in the hCA II-EZM active site. EZM hydration water chain spans D2O molecules W1–W4 and W6. 2FO-FC neutron-scattering length density map is contoured at 1.5 σ level. Structure 2018 26, 383-390.e3DOI: (10.1016/j.str.2018.01.006) Copyright © 2018 Terms and Conditions