Structural comparison of protiated, H/D-exchanged and deuterated human carbonic anhydrase IX.

ABSTRACT: Human carbonic anhydrase IX (CA IX) expression is upregulated in hypoxic solid tumours, promoting cell survival and metastasis. This observation has made CA IX a target for the development of CA isoform-selective inhibitors. To enable structural studies of CA IX-inhibitor complexes using X-ray and neutron crystallography, a CA IX surface variant (CA IX_SV; the catalytic domain with six surface amino-acid substitutions) has been developed that can be routinely crystallized. Here, the preparation of protiated (H/H), H/D-exchanged (H/D) and deuterated (D/D) CA IX_SV for crystallographic studies and their structural comparison are described. Four CA IX_SV X-ray crystal structures are compared: two H/H crystal forms, an H/D crystal form and a D/D crystal form. The

SUBMITTER: Koruza K 

PROVIDER: S-EPMC6778848 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature