1cnx

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spinqualitylabelsall models 1cnx, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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

1CNX is a Single protein structure of sequence from Homo sapiens with ZN, HG and EG2 as ligands. 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

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