1cnw
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | A series of competitive inhibitors of carbonic anhydrase II (CAII; EC | + | 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). |
==Disease== | ==Disease== | ||
| Line 18: | Line 18: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Boriack, P | + | [[Category: Boriack, P A.]] |
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
[[Category: EG1]] | [[Category: EG1]] | ||
[[Category: HG]] | [[Category: HG]] | ||
| Line 25: | Line 25: | ||
[[Category: lyase (oxo-acid)]] | [[Category: lyase (oxo-acid)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:08:02 2008'' |
Revision as of 10:08, 21 February 2008
|
SECONDARY INTERACTIONS SIGNIFICANTLY REMOVED FROM THE SULFONAMIDE BINDING POCKET OF CARBONIC ANHYDRASE II INFLUENCE BINDING CONSTANTS
Contents |
Overview
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).
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
1CNW is a Single protein structure of sequence from Homo sapiens with , and as ligands. The following page contains interesting information on the relation of 1CNW with [Carbonic Anhydrase]. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Secondary interactions significantly removed from the sulfonamide binding pocket of carbonic anhydrase II influence inhibitor binding constants., Boriack PA, Christianson DW, Kingery-Wood J, Whitesides GM, J Med Chem. 1995 Jun 23;38(13):2286-91. PMID:7608893
Page seeded by OCA on Thu Feb 21 12:08:02 2008
