1CNY

SECONDARY INTERACTIONS SIGNIFICANTLY REMOVED FROM THE SULFONAMIDE BINDING POCKET OF CARBONIC ANHYDRASE II INFLUENCE BINDING CONSTANTS

Summary for 1CNY

• Entry DOI: 10.2210/pdb1cny/pdb
• Descriptor: CARBONIC ANHYDRASE II, ZINC ION, MERCURY (II) ION, ... (5 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: 30033.62

Authors

Boriack, P.A.,Christianson, D.W. (deposition date: 1995-07-21, release date: 1995-11-14, Last modification date: 2024-02-07)

Primary citation

Boriack, P.A.,Christianson, D.W.,Kingery-Wood, J.,Whitesides, G.M.
Secondary interactions significantly removed from the sulfonamide binding pocket of carbonic anhydrase II influence inhibitor binding constants.
J.Med.Chem., 38:2286-2291, 1995

PubMed Abstract: A series of competitive inhibitors of carbonic anhydrase II (CAII; EC 4.2.1.1) that consists of oligo(ethylene glycol) units attached to p-benzenesulfonamides with pendant amino acids, H2NSO2C6H4CONHCH2CH2OCH2CH2OCH2CH2NHCOCHRNH3+, have been synthesized and examined using competitive fluorescence assays. Three of the strongest inhibitors, designated EG3NH3+, EG3GlyNH3+, and EG3PheNH3+, have been studied by X-ray crystallographic methods at limiting resolutions of 1.9, 2.0, and 2.3 A, respectively. The sulfonamide-zinc binding modes and the association of the ethylene glycol linkers to the hydrophobic patch of the active site are similar in all three inhibitors. Differences in the values of Kd are therefore not due to differences in zinc coordination or to differences in the modes of enzyme-glycol association but instead appear to arise from interaction of the pendant amino acids with the surface of the protein. These pendant groups are, however, not sufficiently ordered to be visible in electron density maps. Thus, structural variations of inhibitors at locations distant from the primary binding (i.e., the sulfonamide group) site affect the overall binding affinities of inhibitors (e.g., Kd (EG3PheNH3+) = 14 nM as compared with Kd (EG3GluNH3+) = 100 nM).

PubMed: 7608893
DOI: 10.1021/jm00013a004

Experimental method

X-RAY DIFFRACTION (2.3 Å)