6RQQ

X-ray crystal structure of protiated (H) large monoclinic unit cell CA IX SV.

Summary for 6RQQ

• Entry DOI: 10.2210/pdb6rqq/pdb
• Descriptor: Carbonic anhydrase 9, ZINC ION, FORMIC ACID, ... (4 entities in total)
• Functional Keywords: carbonic anhydrase, ca ix, surface variant, proton transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 56408.03

Authors

Fisher, Z.,Koruza, K. (deposition date: 2019-05-16, release date: 2019-09-11, Last modification date: 2024-01-24)

Primary citation

Koruza, K.,Lafumat, B.,Nyblom, M.,Mahon, B.P.,Knecht, W.,McKenna, R.,Fisher, S.Z.
Structural comparison of protiated, H/D-exchanged and deuterated human carbonic anhydrase IX.
Acta Crystallogr D Struct Biol, 75:895-903, 2019

PubMed 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; 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 for crystallographic studies and their structural comparison are described. Four CA IX X-ray crystal structures are compared: two H/H crystal forms, an H/D crystal form and a D/D crystal form. The overall active-site organization in each version is essentially the same, with only minor positional changes in active-site solvent, which may be owing to deuteration and/or resolution differences. Analysis of the crystal contacts and packing reveals different arrangements of CA IX compared with previous reports. To our knowledge, this is the first report comparing three different deuterium-labelled crystal structures of the same protein, marking an important step in validating the active-site structure of CA IX for neutron protein crystallography.

PubMed: 31588921
DOI: 10.1107/S2059798319010027

Experimental method

X-RAY DIFFRACTION (1.276 Å)