1RJ5

Crystal Structure of the Extracellular Domain of Murine Carbonic Anhydrase XIV

Summary for 1RJ5

• Entry DOI: 10.2210/pdb1rj5/pdb
• Related: 1RJ6
• Descriptor: Carbonic anhydrase XIV, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: beta-sheet, alpha-helix, zinc enzyme, lyase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 59962.01

Authors

Whittington, D.A.,Grubb, J.H.,Waheed, A.,Shah, G.N.,Sly, W.S.,Christianson, D.W. (deposition date: 2003-11-18, release date: 2004-03-09, Last modification date: 2024-10-16)

Primary citation

Whittington, D.A.,Grubb, J.H.,Waheed, A.,Shah, G.N.,Sly, W.S.,Christianson, D.W.
Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes.
J.Biol.Chem., 279:7223-7228, 2004

PubMed Abstract: 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.

PubMed: 14660577
DOI: 10.1074/jbc.M310809200

Experimental method

X-RAY DIFFRACTION (2.81 Å)