Structure of cobalt carbonic anhydrase complexed with bicarbonate.
The three-dimensional structure of a complex between catalytically active cobalt(II) substituted human carbonic anhydrase II and its substrate bicarbonate was determined by X-ray crystallography (1.9 A). One water molecule and two bicarbonate oxygen atoms are found at distances between 2.3 and 2.5 A from the cobalt ion in addition to the three histidyl ligands contributed by the peptide chain. The tetrahedral geometry around the metal ion in the native enzyme with a single water molecule 2.0 A from the metal is therefore lost. The geometry is difficult to classify but might best be described as distorted octahedral. The structure is suggested to represent a water-bicarbonate exchange state relevant also for native carbonic anhydrase, where the two unprotonized oxygen atoms of the substrate are bound in a carboxylate binding site and the hydroxyl group is free to move closer to the metal thereby replacing the metal-bound water molecule. A reaction mechanism based on crystallographically determined enzyme-ligand complexes is represented.
Håkansson
K
K
Molecular Biophysics, Chemical Center, University of Lund, Sweden.
Wehnert
A
A
D001639:Bicarbonates / Q000737:chemistry* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D003035:Cobalt / Q000737:chemistry*; D003460:Crystallization; D004950:Esterases / Q000032:analysis; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D011487:Protein Conformation; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D001639:Bicarbonates; D014867:Water; D003035:Cobalt; D006639:Histidine; D004950:Esterases; D002256:Carbonic Anhydrases; D010100:Oxygen