Role of zinc in catalytic activity of carbonic anhydrase IX.
Article Details
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Tu C, Foster L, Alvarado A, McKenna R, Silverman DN, Frost SC
Role of zinc in catalytic activity of carbonic anhydrase IX.
Arch Biochem Biophys. 2012 May;521(1-2):90-4. doi: 10.1016/j.abb.2012.03.017. Epub 2012 Mar 23.
- PubMed ID
- 22465027 [ View in PubMed]
- Abstract
The carbonic anhydrases (CAs) in the alpha class are zinc-dependent metalloenzymes. Previous studies have reported that recombinant forms of carbonic anhydrase IX (CAIX), a membrane-bound form of CA expressed in solid tumors, appear to be activated by low levels of zinc independent of its well-studied role at the catalytic site. In this study, we sought to determine if CAIX is stimulated by zinc in its native environment. MDA-MB-231 breast cancer cells express CAIX in response to hypoxia. We compared CAIX activity associated with membrane ghosts isolated from hypoxic cells with that in intact hypoxic cells. We measured CA activity directly using (18)O exchange from (13)CO(2) into water determined by membrane inlet mass spectrometry. In membrane ghosts, there was little effect of zinc at low concentrations on CAIX activity, although at high concentration zinc was inhibitory. In intact cells, zinc had no significant effect on CAIX activity. This suggests that there is an appreciable decrease in sensitivity to zinc when CAIX is in its natural membrane milieu compared to the purified forms.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Zinc acetate Carbonic anhydrase 1 Protein Humans UnknownLigandDetails