1CAK

STRUCTURAL ANALYSIS OF THE ZINC HYDROXIDE-THR 199-GLU 106 HYDROGEN BONDING NETWORK IN HUMAN CARBONIC ANHYDRASE II

Summary for 1CAK

• Entry DOI: 10.2210/pdb1cak/pdb
• Descriptor: CARBONIC ANHYDRASE II, ZINC ION, SULFATE ION, ... (4 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: 29383.76

Authors

Xue, Y.,Liljas, A.,Jonsson, B.-H.,Lindskog, S. (deposition date: 1992-09-17, release date: 1993-10-31, Last modification date: 2024-02-07)

Primary citation

Xue, Y.,Liljas, A.,Jonsson, B.H.,Lindskog, S.
Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II.
Proteins, 17:93-106, 1993

PubMed Abstract: 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.

PubMed: 7901850
DOI: 10.1002/prot.340170112

Experimental method

X-RAY DIFFRACTION (1.9 Å)