|1rj6, resolution 2.90Å ()|
|Ligands:||, , , ,|
|Gene:||CA14, CAR14, CATM (Mus musculus)|
Crystal Structure of the Extracellular Domain of Murine Carbonic Anhydrase XIV in Complex with Acetazolamide
Carbonic anhydrase (CA) XIV is the most recently identified mammalian carbonic anhydrase isozyme, and its presence has been demonstrated in a number of tissues. Full-length CA XIV is a transmembrane protein composed of an extracellular catalytic domain, a single transmembrane helix, and a short intracellular polypeptide segment. The amino acid sequence identity of human CA XIV relative to the other membrane-associated isozymes (CA IV, CA IX, and CA XII) is 34-46%. We report here the expression and purification of both the full-length enzyme and a truncated, secretory form of murine CA XIV. Both forms of this isozyme are highly active, and both show an abrogation of activity in the presence of 0.2% SDS, in contrast to the behavior of murine CA IV. We also report the crystal structure of the extracellular domain of murine CA XIV at 2.8 A resolution and of an enzyme-acetazolamide complex at 2.9 A resolution. The structure shows a monomeric glycoprotein with a topology similar to that of other mammalian CA isozymes. Based on the x-ray crystallographic results, we compare and contrast known structures of membrane-associated CA isozymes to rationalize the structural elements responsible for the SDS resistance of CA IV and to discuss prospects for the design of selective inhibitors of membrane-associated CA isozymes.
Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes., Whittington DA, Grubb JH, Waheed A, Shah GN, Sly WS, Christianson DW, J Biol Chem. 2004 Feb 20;279(8):7223-8. Epub 2003 Dec 3. PMID:14660577
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Whittington DA, Grubb JH, Waheed A, Shah GN, Sly WS, Christianson DW. Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes. J Biol Chem. 2004 Feb 20;279(8):7223-8. Epub 2003 Dec 3. PMID:14660577 doi:10.1074/jbc.M310809200