1f2w
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The three-dimensional structure of a possible intermediate in the | + | The three-dimensional structure of a possible intermediate in the hydration reaction of cyanamide to urea catalyzed by human carbonic anhydrase II (hCAII) has been determined by cryocrystallographic techniques. The crystal structure shows that two different adducts are formed under the experimental conditions and that they have different occupancy in the crystal. The high occupancy form consists of a binary hCAII-cyanamide complex where the substrate has replaced the zinc-bound hydroxide anion present in the native enzyme, maintaining the tetrahedral geometry around the metal ion. The second, low-occupancy form consists of a hCAII-cyanamide-water ternary complex where the catalytic zinc ion, still being bound to cyanamide, is approached by a water molecule in a five-coordinate adduct. While the first form can be considered a nonproductive complex, the second form may represent an intermediate state of the catalyzed reaction where the water molecule is about to perform a nucleophilic attack on the zinc-activated cyanamide substrate. The structural evidence is consistent with the kinetic data previously reported about this recently described hydrolytic reaction catalyzed by hCAII, and indicates that a different mechanism with respect to that generally accepted for the physiologic carbon dioxide hydration reaction may be adopted by the enzyme, depending on the substrate chemical properties. |
==Disease== | ==Disease== | ||
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[[Category: Mangani, S.]] | [[Category: Mangani, S.]] | ||
[[Category: Scozzafava, A.]] | [[Category: Scozzafava, A.]] | ||
| - | [[Category: Supuran, C | + | [[Category: Supuran, C T.]] |
[[Category: CNN]] | [[Category: CNN]] | ||
[[Category: HG]] | [[Category: HG]] | ||
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[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:34:13 2008'' |
Revision as of 10:34, 21 February 2008
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THE MECHANISM OF CYANAMIDE HYDRATION CATALYZED BY CARBONIC ANHYDRASE II REVEALED BY CRYOGENIC X-RAY DIFFRACTION
Contents |
Overview
The three-dimensional structure of a possible intermediate in the hydration reaction of cyanamide to urea catalyzed by human carbonic anhydrase II (hCAII) has been determined by cryocrystallographic techniques. The crystal structure shows that two different adducts are formed under the experimental conditions and that they have different occupancy in the crystal. The high occupancy form consists of a binary hCAII-cyanamide complex where the substrate has replaced the zinc-bound hydroxide anion present in the native enzyme, maintaining the tetrahedral geometry around the metal ion. The second, low-occupancy form consists of a hCAII-cyanamide-water ternary complex where the catalytic zinc ion, still being bound to cyanamide, is approached by a water molecule in a five-coordinate adduct. While the first form can be considered a nonproductive complex, the second form may represent an intermediate state of the catalyzed reaction where the water molecule is about to perform a nucleophilic attack on the zinc-activated cyanamide substrate. The structural evidence is consistent with the kinetic data previously reported about this recently described hydrolytic reaction catalyzed by hCAII, and indicates that a different mechanism with respect to that generally accepted for the physiologic carbon dioxide hydration reaction may be adopted by the enzyme, depending on the substrate chemical properties.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
1F2W is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction., Guerri A, Briganti F, Scozzafava A, Supuran CT, Mangani S, Biochemistry. 2000 Oct 10;39(40):12391-7. PMID:11015219
Page seeded by OCA on Thu Feb 21 12:34:13 2008
Categories: Carbonate dehydratase | Homo sapiens | Single protein | Briganti, F. | Guerri, A. | Mangani, S. | Scozzafava, A. | Supuran, C T. | CNN | HG | HGB | ZN | Protein-inhibitor complex
