skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Paramagnetic carbon-13 NMR relaxation studies on the kinetics and mechanism of the HCO/sub 3//sup -//CO/sub 2/ exchange catalyzed by manganese(II) human carbonic anhydrase I

Journal Article · · Biochemistry; (United States)
OSTI ID:6616620

A detailed analysis of the stability and activity of Mn(II) human carbonic anhydrase I and the kinetics and mechanism of its catalysis of the HCO/sub 3//sup -//CO/sub 2/ exchange have been performed at pH 8.5. The analysis was based on the paramagnetic relaxation rates R/sub 1p/ and R/sub 2p/ of the /sup 13/C atom of HCO/sub 3//sup -/ in the Mn/sup 2 +//apoenzyme/HCO/sub 3//sup -//CO/sub 2/ system and the HCO/sub 3//sup -/ in equilibrium CO/sub 2/ interconversion rate obtained by the magnetization-transfer technique. The R/sub 1p/ and R/sub 2p/ rates were measured as functions of the temperature, magnetic field strength, and substrate and apoenzyme concentrations and were interpreted on the basis of Solomon-Bloembergen-Morgan theories and general equations for the liquid exchange. From the analysis of the data, a formation constant for the Mn(II) enzyme of log K/sub MA//sup M/ = 5.8 +/- 0.4 was obtained while the activity of the Mn(II) enzyme, measured as the HCO/sub 3//sup -//CO/sub 2/ interconversion rate at (HCO/sub 3//sup -/) = 0.100 M and pH 8.5, was found to be about 4% of that of the native Zn(II) enzyme. Most conspicuously, the resulting distance of only 2.71 +/- 0.03 A between the Mn/sup 2 +/ ion of the enzyme and the /sup 13/C atom of HCO/sub 3//sup -/ in the enzyme-bicarbonate complex indicates that the bicarbonate is bound to the metal ion by two of its oxygen atoms in the central catalytic step, thereby supporting the modified Zn(II)-OH mechanism. In contrast, this binding mode differs from the structure of the complexes suggested in the rapid-equilibrium kinetic model.

Research Organization:
Univ. of Copenhagen, Denmark
OSTI ID:
6616620
Journal Information:
Biochemistry; (United States), Vol. 26:1
Country of Publication:
United States
Language:
English