1F2W

THE MECHANISM OF CYANAMIDE HYDRATION CATALYZED BY CARBONIC ANHYDRASE II REVEALED BY CRYOGENIC X-RAY DIFFRACTION

Summary for 1F2W

• Entry DOI: 10.2210/pdb1f2w/pdb
• Related: 1BV3
• Descriptor: CARBONIC ANHYDRASE II, ZINC ION, MERCURY (II) ION, ... (6 entities in total)
• Functional Keywords: protein-inhibitor complex, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29804.61

Authors

Guerri, A.,Briganti, F.,Scozzafava, A.,Supuran, C.T.,Mangani, S. (deposition date: 2000-05-30, release date: 2000-06-08, Last modification date: 2024-02-07)

Primary citation

Guerri, A.,Briganti, F.,Scozzafava, A.,Supuran, C.T.,Mangani, S.
Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction.
Biochemistry, 39:12391-12397, 2000

PubMed Abstract: 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.

PubMed: 11015219
DOI: 10.1021/bi000937c

Experimental method

X-RAY DIFFRACTION (1.9 Å)