1HK0

Human GammaD Crystallin Structure at 1.25 A Resolution

1HK0 の概要

• エントリーDOI: 10.2210/pdb1hk0/pdb
• 関連するPDBエントリー: 1H4A 1LD0
• 分子名称: Gamma-crystallin D (2 entities in total)
• 機能のキーワード: eye lens protein, cataract
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20634.97

構造登録者

Basak, A.K.,Slingsby, C. (登録日: 2003-03-05, 公開日: 2003-05-08, 最終更新日: 2023-12-13)

主引用文献

Basak, A.K.,Bateman, O.,Slingsby, C.,Pande, A.,Asherie, N.,Ogun, O.,Benedek, G.,Pande, J.
High-Resolution X-Ray Crystal Structures of Human Gammad Crystallin (1.25A) and the R58H Mutant (1.15A) Associated with Aculeiform Cataract
J.Mol.Biol., 328:1137-1147, 2003

PubMed Abstract: 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.

PubMed: 12729747
DOI: 10.1016/S0022-2836(03)00375-9

実験手法

X-RAY DIFFRACTION (1.25 Å)