1HUG

Differences in anionic inhibition of Human Carbonic Anhydrase I revealed from the structures of iodide and gold cyanide inhibitor complexes


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Observed: 0.171 

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This is version 1.4 of the entry. See complete history


Literature

Differences in anionic inhibition of human carbonic anhydrase I revealed from the structures of iodide and gold cyanide inhibitor complexes.

Kumar, V.Kannan, K.K.Sathyamurthi, P.

(1994) Acta Crystallogr D Biol Crystallogr 50: 731-738

  • DOI: https://doi.org/10.1107/S0907444994001873
  • Primary Citation of Related Structures:  
    1HUG, 1HUH

  • PubMed Abstract: 

    The crystal structures of two anionic inhibitor complexes of human carbonic anhydrase I (HCAI), namely, HCAI-iodide and HCAI-Au(CN)(2)(-), have been refined by the restrained least-squares method at 2.2 and 2 A nominal resolution, respectively, with good stereochemistry for the final models. The R values have improved from 30.3 to 16.6% for HCAI-iodide and from 28.8 to 17.1% for HCAI-Au(CN)(2)(-). The sites of inhibitor binding as elucidated are totally different in the two structures. The iodide anion replaces the zinc-bound H(2)O/OH(-) ligand and renders the enzyme inactive. This result confirms that the zinc-bound H(2)O/OH(-) is the activity-linked group in carbonic anhydrase enzymes. Au(CN)(2)(-) binds at a different and new site near the zinc ion, without liganding to the metal. The N atom of Au(CN)(2)(-) is within hydrogen-bonding distance of the zinc-bound H(2)O/OH(-) group which shifts by about 0.4 A away from the zinc ion in relation to its position in the native HCAI. It is proposed that the presence of the inhibitor Au(CN)(2)(-) results in a conformational reorientation of the activity-linked group, due to hydrogen-bond formation with the inhibitor, which in turn sterically hinders the binding of the substrate CO(2) molecule in the active site, leading to the inhibition of HCAI enzyme.


  • Organizational Affiliation

    Solid State Physics Division, Bhabha Atomic Research Centre, Bombay, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CARBONIC ANHYDRASE I260Homo sapiensMutation(s): 0 
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00915 (Homo sapiens)
Explore P00915 
Go to UniProtKB:  P00915
PHAROS:  P00915
GTEx:  ENSG00000133742 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00915
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Observed: 0.171 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 81.8α = 90
b = 75.2β = 90
c = 37.1γ = 90
Software Package:
Software NamePurpose
PROLSQrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1994-04-30
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-11-29
    Changes: Derived calculations, Other
  • Version 1.4: 2024-02-07
    Changes: Data collection, Database references, Derived calculations