1rj5: Difference between revisions

Revision as of 15:51, 21 February 2008

Crystal Structure of the Extracellular Domain of Murine Carbonic Anhydrase XIV

OverviewOverview

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 StructureAbout this Structure

1RJ5 is a Single protein structure of sequence from Mus musculus with , and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.

ReferenceReference

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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-[[Image:1rj5.jpg|left|200px]]<br /><applet load="1rj5" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1rj5.jpg|left|200px]]<br /><applet load="1rj5" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1rj5, resolution 2.81&Aring;" />
 '''Crystal Structure of the Extracellular Domain of Murine Carbonic Anhydrase XIV'''<br />
 ==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.
+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==
-RJ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN, CL and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RJ5 OCA].
+RJ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RJ5 OCA].
 ==Reference==
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 [[Category: Mus musculus]]
 [[Category: Single protein]]
-[[Category: Christianson, D.W.]]
+[[Category: Christianson, D W.]]
-[[Category: Grubb, J.H.]]
+[[Category: Grubb, J H.]]
-[[Category: Shah, G.N.]]
+[[Category: Shah, G N.]]
-[[Category: Sly, W.S.]]
+[[Category: Sly, W S.]]
 [[Category: Waheed, A.]]
-[[Category: Whittington, D.A.]]
+[[Category: Whittington, D A.]]
 [[Category: ACY]]
 [[Category: CL]]
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 [[Category: zinc enzyme]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:38:17 2007''
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