1lgd

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spinqualitylabelsall models 1lgd, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure Analysis of HCA II Mutant T199P in Complex with Bicarbonate

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Substitution of Pro for Thr199 in the active site of human carbonic, anhydrase II (HCA II)(1) reduces its catalytic efficiency about 3000-fold., X-ray crystallographic structures of the T199P/C206S variant have been, determined in complex with the substrate bicarbonate and with the, inhibitors thiocyanate and beta-mercaptoethanol. The latter molecule is, normally not an inhibitor of wild-type HCA II. All three ligands display, novel binding interactions to the T199P/C206S mutant. The, beta-mercaptoethanol molecule binds in the active site area with its, sulfur atom tetrahedrally coordinated to the zinc ion. Thiocyanate binds, tetrahedrally coordinated to the zinc ion in T199P/C206S, in contrast to, its pentacoordinated binding to the zinc ion in wild-type HCA II., Bicarbonate binds to the mutant with two of its oxygens at the positions, of the zinc water (Wat263) and Wat318 in wild-type HCA II. The environment, of this area is more hydrophilic than the normal bicarbonate-binding site, of HCA II situated in the hydrophobic part of the cavity normally occupied, by the so-called deep water (Wat338). The observation of a new binding, site for bicarbonate has implications for understanding the mechanism by, which the main-chain amino group of Thr199 acquired an important role for, orientation of the substrate during the evolution of the enzyme.

Disease

Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]

About this Structure

1LGD is a Single protein structure of sequence from Homo sapiens with ZN and BCT as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.

Reference

Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-function studies of a T199P/C206S mutant., Huang S, Sjoblom B, Sauer-Eriksson AE, Jonsson BH, Biochemistry. 2002 Jun 18;41(24):7628-35. PMID:12056894

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