1hk0

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spinqualitylabelsall models 1hk0, resolution 1.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HUMAN GAMMA-D CRYSTALLIN STRUCTURE AT 1.25 A RESOLUTION

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Several human cataracts have been linked to mutations in the gamma, crystallin gene. One of these is the aculeiform cataract, which is caused, by an R58H mutation in gammaD crystallin. We have shown previously that, this cataract is caused by crystallization of the mutant protein, which is, an order of magnitude less soluble than the wild-type. Here, we report the, very high-resolution crystal structures of the mutant and wild-type, proteins. Both proteins crystallize in the same space group and lattice., Thus, a strict comparison of the protein-protein and protein-water, intermolecular interactions in the two crystal lattices is possible., Overall, the differences between the mutant and wild-type structures are, small. At position 58, the mutant protein loses the direct ion-pair, intermolecular interaction present in the wild-type, due to the, differences between histidine and arginine at the atomic level; the, interaction in the mutant is mediated by water molecules. Away from the, mutation site, the mutant and wild-type lattice structures differ in the, identity of side-chains that occupy alternate conformations. Since the, interactions in the crystal phase are very similar for the two proteins, we conclude that the reduction in the solubility of the mutant is mainly, due to the effect of the R58H mutation in the solution phase. The results, presented here are also important as they are the first high-resolution, X-ray structures of human gamma crystallins.

Disease

Known diseases associated with this structure: Cataract, congenital, cerulean type, 3 OMIM:[123690], Cataract, crystalline aculeiform OMIM:[123690], Cataract, nonnuclear polymorphic congenital OMIM:[123690], Cataracts, punctate, progressive juvenile-onset OMIM:[123690]

About this Structure

1HK0 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

High-resolution X-ray crystal structures of human gammaD crystallin (1.25 A) and the R58H mutant (1.15 A) associated with aculeiform cataract., Basak A, Bateman O, Slingsby C, Pande A, Asherie N, Ogun O, Benedek GB, Pande J, J Mol Biol. 2003 May 16;328(5):1137-47. PMID:12729747

Page seeded by OCA on Mon Nov 12 17:19:01 2007