4E5Q

Human Carbonic Anhydrase II in complex with cyanate

Summary for 4E5Q

• Entry DOI: 10.2210/pdb4e5q/pdb
• Related: 2ILI 3D92
• Descriptor: Carbonic anhydrase 2, ZINC ION, cyanic acid, ... (4 entities in total)
• Functional Keywords: mixed alpha beta protein, enzyme proton transfer, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29397.50

Authors

West, D.,McKenna, R. (deposition date: 2012-03-14, release date: 2013-03-27, Last modification date: 2023-09-13)

Primary citation

West, D.,Pinard, M.A.,Tu, C.,Silverman, D.N.,McKenna, R.
Human carbonic anhydrase II-cyanate inhibitor complex: putting the debate to rest.
Acta Crystallogr F Struct Biol Commun, 70:1324-1327, 2014

PubMed Abstract: The binding of anions to carbonic anhydrase II (CA II) has been attributed to high affinity for the active-site zinc. An anion of interest is cyanate, for which contrasting binding modes have been reported in the literature. Previous spectroscopic data have shown cyanate behaving as an inhibitor, directly binding to the zinc, in contrast to previous crystallographic data that implied that cyanate acts as a substrate mimic that is not directly bound to the zinc but overlaps with the binding site of the substrate CO2. Wild-type and the V207I variant of CA II have been expressed and X-ray crystal structures of their cyanate complexes have been determined to 1.7 and 1.5 Å resolution, respectively. The rationale for the V207I CA II variant was its close proximity to the CO2-binding site. Both structures clearly show that the cyanate binds directly to the zinc. In addition, inhibition constants (∼40 µM) were measured using (18)O-exchange mass spectrometry for wild-type and V207I CA II and were similar to those determined previously (Supuran et al., 1997). Hence, it is concluded that under the conditions of these experiments the binding of cyanate to CA II is directly to the zinc, displacing the zinc-bound solvent molecule, and not in a site that overlaps with the CO2 substrate-binding site.

PubMed: 25286933
DOI: 10.1107/S2053230X14018135

Experimental method

X-RAY DIFFRACTION (1.7024 Å)