1rj6
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(New page: 200px<br /><applet load="1rj6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rj6, resolution 2.90Å" /> '''Crystal Structure of...)
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Revision as of 23:31, 20 November 2007
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Crystal Structure of the Extracellular Domain of Murine Carbonic Anhydrase XIV in Complex with Acetazolamide
Overview
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.
About this Structure
1RJ6 is a Single protein structure of sequence from Mus musculus with ZN and AZM as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
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
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