Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/4233
Title: Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine
Authors: F., Briganti
Mangani, Stefano 
P., Orioli
A., Scozzafava
G., Vernaglione
C. T., Supuran
Keywords: human carbonic anhydrase; crystal structure; histamine; activator
Issue Date: 1997
Project: None 
Journal: BIOCHEMISTRY
Abstract: 
The interaction of native and Co(II)-substituted isozymes I and II of carbonic anhydrase (CA) with histamine, a well-known activator, was investigated kinetically, spectroscopically, and X-ray crystallographically. This activator is of the noncompetitive type with 4-nitrophenyl acetate and CO2, as substrates for both HCA I and HCA II. The electronic spectrum of the adduct of Co(II)-HCA II with histamine is similar to the spectrum of the Co(II)-HCA II-phenol adduct, being only slightly different from that of the uncomplexed enzyme. This is the first spectroscopic evidence that the activator molecule binds within the active site, but not directly to the metal ion. X-ray crystallographic data for the adduct of HCA II with histamine showed that the activator molecule is bound at the entrance of the active site cavity in a position where it may actively participate in shuttling protons between the active site and the hulk solvent. The role of the activators and the reported X-ray crystal structure of the HCA II-histamine adduct has prompted us to reexamine the X-ray structures of the different CA isozymes in elder to find a structural basis accounting for their large differences in catalytic rate. A tentative explanation is proposed on the basis of possible pathways of proton transfer, which constitute the rate-limiting step in the catalytic reaction.
Description: 
47974
URI: http://hdl.handle.net/20.500.12779/4233
ISSN: 0006-2960
DOI: 10.1021/bi970760v
Appears in Collections:Publications

Show full item record

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.