1AVN

HUMAN CARBONIC ANHYDRASE II COMPLEXED WITH THE HISTAMINE ACTIVATOR

Summary for 1AVN

• Entry DOI: 10.2210/pdb1avn/pdb
• Descriptor: CARBONIC ANHYDRASE II, ZINC ION, MERCURY (II) ION, ... (6 entities in total)
• Functional Keywords: lyase, oxo-acid
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29577.03

Authors

Briganti, F.,Mangani, S.,Orioli, P.,Scozzafava, A.,Vernaglione, G.,Supuran, C.T. (deposition date: 1997-09-17, release date: 1997-12-24, Last modification date: 2024-02-07)

Primary citation

Briganti, F.,Mangani, S.,Orioli, P.,Scozzafava, A.,Vernaglione, G.,Supuran, C.T.
Carbonic anhydrase activators: X-ray crystallographic and spectroscopic investigations for the interaction of isozymes I and II with histamine.
Biochemistry, 36:10384-10392, 1997

PubMed 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 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.

PubMed: 9265618
DOI: 10.1021/bi970760v

Experimental method

X-RAY DIFFRACTION (2 Å)