Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/4495
Title: Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction
Authors: A., Guerri
F., Briganti
A., Scozzafava
C. T., Supuran
Mangani, Stefano 
Keywords: x-ray; crystal structure; human carbonic anhydrase; cyanamide
Issue Date: 2000
Project: None 
Journal: BIOCHEMISTRY
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.
Description: 
47958
URI: http://hdl.handle.net/20.500.12779/4495
ISSN: 0006-2960
DOI: 10.1021/bi000937c
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