1cam
STRUCTURAL ANALYSIS OF THE ZINC HYDROXIDE-THR 199-GLU 106 HYDROGEN BONDING NETWORK IN HUMAN CARBONIC ANHYDRASE II
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OverviewOverview
The significance of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond, network in the active site of human carbonic anhydrase II has been, examined by X-ray crystallographic analyses of site-specific mutants., Mutants with Ala-199 and Ala-106 or Gln-106 have low catalytic activities, while a mutant with Asp-106 has almost full CO2 hydration activity. The, structures of these four mutants, as well as that of the bicarbonate, complex of the mutant with Ala-199, have been determined at 1.7 to 2.2 A, resolution. Removal of the gamma atoms of residue 199 leads to a distorted, tetrahedral geometry at the zinc ion, and a catalytically important, zinc-bound water molecule has moved towards Glu-106. In the bicarbonate, complex of the mutant with Ala-199 one oxygen atom from bicarbonate binds, to zinc without displacing this water molecule. Tetrahedral coordination, geometries are retained in the mutants at position 106. The mutants with, Ala-106 and Gln-106 have a zinc-bound sulfate ion, whereas this sulfate, site is only partially occupied in the mutant with Asp-106. The, hydrogen-bond network seems to be "reversed" in the mutants with Ala-106, and Gln-106. The network is preserved as in native enzyme in the mutant, with Asp-106 but the side chain of Asp-106 is more extended than that of, Glu-106 in the native enzyme. These results illustrate the importance of, Glu-106 and Thr-199 for controlling the precise coordination geometry of, the zinc ion and its ligand preferences which results in an optimal, orientation of a zinc-bound hydroxide ion for an attack on the CO2, substrate.
DiseaseDisease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this StructureAbout this Structure
1CAM is a Single protein structure of sequence from Homo sapiens with ZN and BCT as ligands. The following page contains interesting information on the relation of 1CAM with [Carbonic Anhydrase]. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II., Xue Y, Liljas A, Jonsson BH, Lindskog S, Proteins. 1993 Sep;17(1):93-106. PMID:7901850
Page seeded by OCA on Mon Nov 12 16:19:25 2007