1HUH

DIFFERENCES IN ANIONIC INHIBITION OF HUMAN CARBONIC ANHYDRASE I REVEALED FROM THE STRUCTURES OF IODIDE AND GOLD CYANIDE INHIBITOR COMPLEXES

Summary for 1HUH

• Entry DOI: 10.2210/pdb1huh/pdb
• Descriptor: CARBONIC ANHYDRASE I, ZINC ION, IODIDE ION, ... (4 entities in total)
• Functional Keywords: lyase(oxo-acid)
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P00915
• Total number of polymer chains: 1
• Total formula weight: 29474.92

Authors

Kumar, V.,Kannan, K.K. (deposition date: 1993-10-28, release date: 1994-04-30, Last modification date: 2024-02-07)

Primary citation

Kumar, V.,Kannan, K.K.,Sathyamurthi, P.
Differences in anionic inhibition of human carbonic anhydrase I revealed from the structures of iodide and gold cyanide inhibitor complexes.
Acta Crystallogr.,Sect.D, 50:731-738, 1994

PubMed Abstract: 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.

PubMed: 15299369
DOI: 10.1107/S0907444994001873

Experimental method

X-RAY DIFFRACTION (2.2 Å)