1hug: Difference between revisions
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New page: left|200px<br /> <applet load="1hug" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hug, resolution 2.0Å" /> '''DIFFERENCES IN ANION... |
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[[Image:1hug.gif|left|200px]]<br /> | [[Image:1hug.gif|left|200px]]<br /><applet load="1hug" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1hug" size=" | |||
caption="1hug, resolution 2.0Å" /> | caption="1hug, resolution 2.0Å" /> | ||
'''DIFFERENCES IN ANIONIC INHIBITION OF HUMAN CARBONIC ANHYDRASE I REVEALED FROM THE STRUCTURES OF IODIDE AND GOLD CYANIDE INHIBITOR COMPLEXES'''<br /> | '''DIFFERENCES IN ANIONIC INHIBITION OF HUMAN CARBONIC ANHYDRASE I REVEALED FROM THE STRUCTURES OF IODIDE AND GOLD CYANIDE INHIBITOR COMPLEXES'''<br /> | ||
==Overview== | ==Overview== | ||
The crystal structures of two anionic inhibitor complexes of human | The crystal structures of two anionic inhibitor complexes of human carbonic anhydrase I (HCAI), namely, HCAI-iodide and HCAI-Au(CN)(2)(-), have been refined by the restrained least-squares method at 2.2 and 2 A nominal resolution, respectively, with good stereochemistry for the final models. The R values have improved from 30.3 to 16.6% for HCAI-iodide and from 28.8 to 17.1% for HCAI-Au(CN)(2)(-). The sites of inhibitor binding as elucidated are totally different in the two structures. The iodide anion replaces the zinc-bound H(2)O/OH(-) ligand and renders the enzyme inactive. This result confirms that the zinc-bound H(2)O/OH(-) is the activity-linked group in carbonic anhydrase enzymes. Au(CN)(2)(-) binds at a different and new site near the zinc ion, without liganding to the metal. The N atom of Au(CN)(2)(-) is within hydrogen-bonding distance of the zinc-bound H(2)O/OH(-) group which shifts by about 0.4 A away from the zinc ion in relation to its position in the native HCAI. It is proposed that the presence of the inhibitor Au(CN)(2)(-) results in a conformational reorientation of the activity-linked group, due to hydrogen-bond formation with the inhibitor, which in turn sterically hinders the binding of the substrate CO(2) molecule in the active site, leading to the inhibition of HCAI enzyme. | ||
==About this Structure== | ==About this Structure== | ||
1HUG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and AUC 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:// | 1HUG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=AUC:'>AUC</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=1HUG OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Kannan, K | [[Category: Kannan, K K.]] | ||
[[Category: Kumar, V.]] | [[Category: Kumar, V.]] | ||
[[Category: AUC]] | [[Category: AUC]] | ||
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[[Category: lyase(oxo-acid)]] | [[Category: lyase(oxo-acid)]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:04:57 2008'' | ||
