Neutron structure of human carbonic anhydrase II in complex with methazolamide: mapping the solvent and hydrogen-bonding patterns of an effective clinical drug.

ABSTRACT: Carbonic anhydrases (CAs; EC 4.2.1.1) catalyze the interconversion of CO₂ and HCO₃^-, and their inhibitors have long been used as diuretics and as a therapeutic treatment for many disorders such as glaucoma and epilepsy. Acetazolamide (AZM) and methazolamide (MZM, a methyl derivative of AZM) are two of the classical CA inhibitory drugs that have been used clinically for decades. The jointly refined X-ray/neutron structure of MZM in complex with human CA isoform II (hCA II) has been determined to a resolution of 2.2 Å with an R_cryst of ∼16.0%. Presented in this article, along with only the second neutron structure of a clinical drug-bound hCA, is an in-depth structural comparison and analyses of differences in hydrogen-bonding network, water

SUBMITTER: Aggarwal M 

PROVIDER: S-EPMC5391854 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature