1avn
From Proteopedia
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HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH THE HISTAMINE ACTIVATOR
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Overview
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, bulk 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 order 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.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
1AVN is a Single protein structure of sequence from Homo sapiens with ZN, HG, AZI and HSM as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine., Briganti F, Mangani S, Orioli P, Scozzafava A, Vernaglione G, Supuran CT, Biochemistry. 1997 Aug 26;36(34):10384-92. PMID:9265618
Page seeded by OCA on Tue Dec 18 14:22:03 2007
Categories: Carbonate dehydratase | Homo sapiens | Single protein | Briganti, F. | Mangani, S. | Orioli, P. | Scozzafava, A. | Supuran, C.T. | Vernaglione, G. | AZI | HG | HSM | ZN | Lyase | Oxo-acid