The structures of human carbonic-anhydrase-II complexes with the anionic inhibitors hydrogen sulphide (HS-) and nitrate (NO3-) have been determined by X-ray diffraction at 0.19-nm resolution from crystals soaked at pH 7.8 and 6.0, respectively. The modes of binding of these two anions differ markedly from each other. The strong inhibitor HS- replaces the native zinc-bound water/hydroxide (Wat263) leaving the tetrahedral metal geometry unaltered and acts as a hydrogen-bonding donor towards Thr199gamma. The weak NO3- inhibitor does not displace Wat263 from the metal coordination but occupies a fifth binding site changing the zinc coordination polyhedron into a slightly distorted trigonal bipyramid. The interaction of NO3- with the metal is weak; the nearest of its oxygen atoms being at a distance of 0.28 nm from the zinc ion. The binding of nitrate to the enzyme is completed by a hydrogen bond to the metal coordinated Wat263 and a second one to a water molecule of the active-site cavity. The structures of the two complexes help to rationalize the binding of anionic inhibitors to carbonic anhydrase and the binding mode displayed by NO3- may be relevant to the catalytic mechanism.

Mangani, S., & K., H. (1992). Crystallographic Studies of the Binding of Protonated and Unprotonated Inhibitors To Carbonic-anhydrase Using Hydrogen-sulfide and Nitrate Anions. EUROPEAN JOURNAL OF BIOCHEMISTRY, 210, 867-871 [10.1111/j.1432-1033.1992.tb17490.x].

Crystallographic Studies of the Binding of Protonated and Unprotonated Inhibitors To Carbonic-anhydrase Using Hydrogen-sulfide and Nitrate Anions

MANGANI, STEFANO;
1992

Abstract

The structures of human carbonic-anhydrase-II complexes with the anionic inhibitors hydrogen sulphide (HS-) and nitrate (NO3-) have been determined by X-ray diffraction at 0.19-nm resolution from crystals soaked at pH 7.8 and 6.0, respectively. The modes of binding of these two anions differ markedly from each other. The strong inhibitor HS- replaces the native zinc-bound water/hydroxide (Wat263) leaving the tetrahedral metal geometry unaltered and acts as a hydrogen-bonding donor towards Thr199gamma. The weak NO3- inhibitor does not displace Wat263 from the metal coordination but occupies a fifth binding site changing the zinc coordination polyhedron into a slightly distorted trigonal bipyramid. The interaction of NO3- with the metal is weak; the nearest of its oxygen atoms being at a distance of 0.28 nm from the zinc ion. The binding of nitrate to the enzyme is completed by a hydrogen bond to the metal coordinated Wat263 and a second one to a water molecule of the active-site cavity. The structures of the two complexes help to rationalize the binding of anionic inhibitors to carbonic anhydrase and the binding mode displayed by NO3- may be relevant to the catalytic mechanism.
Mangani, S., & K., H. (1992). Crystallographic Studies of the Binding of Protonated and Unprotonated Inhibitors To Carbonic-anhydrase Using Hydrogen-sulfide and Nitrate Anions. EUROPEAN JOURNAL OF BIOCHEMISTRY, 210, 867-871 [10.1111/j.1432-1033.1992.tb17490.x].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/34475
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