1hug
From Proteopedia
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DIFFERENCES IN ANIONIC INHIBITION OF HUMAN CARBONIC ANHYDRASE I REVEALED FROM THE STRUCTURES OF IODIDE AND GOLD CYANIDE INHIBITOR COMPLEXES
Overview
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
1HUG is a Single protein structure of sequence from Homo sapiens with ZN and AUC as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Differences in anionic inhibition of human carbonic anhydrase I revealed from the structures of iodide and gold cyanide inhibitor complexes., Kumar V, Kannan KK, Sathyamurthi P, Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):731-8. PMID:15299369
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