Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV

Bioorg Med Chem Lett. 2007 Feb 1;17(3):628-35. doi: 10.1016/j.bmcl.2006.11.027. Epub 2006 Nov 15.

Abstract

The activation of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with L-adrenaline and histamine has been investigated by kinetic and X-ray crystallographic studies. L-Adrenaline behaves as a potent activator of isozyme CA I (activation constant of 90 nM), being a much weaker activator of isozyme CA II (activation constant of 96 microM). Isoforms CA IV, VA, VII, and XIV were activated by L-adrenaline with K(A)s in the range of 36-63 microM. The X-ray crystal structure of the CA II-L-adrenaline adduct revealed that the activator plugs the entrance of the active site cavity, obstructing it almost completely.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / drug effects
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism*
  • Crystallography, X-Ray
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Enzyme Activators / chemical synthesis*
  • Enzyme Activators / pharmacology*
  • Epinephrine / pharmacology*
  • Histamine / pharmacology
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation

Substances

  • Enzyme Activators
  • Isoenzymes
  • Histamine
  • Carbonic Anhydrases
  • Epinephrine

Associated data

  • PDB/2HKK