3S67

Crystal structure of V57P mutant of human cystatin C

3S67 の概要

• エントリーDOI: 10.2210/pdb3s67/pdb
• 関連するPDBエントリー: 1G96 1R4C 1TIJ 3GAX 3NX0
• 分子名称: Cystatin-C, DI(HYDROXYETHYL)ETHER, IMIDAZOLE, ... (6 entities in total)
• 機能のキーワード: hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01034
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14032.24

構造登録者

Orlikowska, M.,Szymanska, A.,Borek, D.,Otwinowski, Z.,Skowron, P.,Jankowska, E. (登録日: 2011-05-25, 公開日: 2012-05-30, 最終更新日: 2024-10-16)

主引用文献

Orlikowska, M.,Szymanska, A.,Borek, D.,Otwinowski, Z.,Skowron, P.,Jankowska, E.
Structural characterization of V57D and V57P mutants of human cystatin C, an amyloidogenic protein.
Acta Crystallogr.,Sect.D, 69:577-586, 2013

PubMed Abstract: Wild-type human cystatin C (hCC wt) is a low-molecular-mass protein (120 amino-acid residues, 13,343 Da) that is found in all nucleated cells. Physiologically, it functions as a potent regulator of cysteine protease activity. While the biologically active hCC wt is a monomeric protein, all crystallization efforts to date have resulted in a three-dimensional domain-swapped dimeric structure. In the recently published structure of a mutated hCC, the monomeric fold was preserved by a stabilization of the conformationally constrained loop L1 caused by a single amino-acid substitution: Val57Asn. Additional hCC mutants were obtained in order to elucidate the relationship between the stability of the L1 loop and the propensity of human cystatin C to dimerize. In one mutant Val57 was substituted by an aspartic acid residue, which is favoured in β-turns, and in the second mutant proline, a residue known for broadening turns, was substituted for the same Val57. Here, 2.26 and 3.0 Å resolution crystal structures of the V57D andV57P mutants of hCC are reported and their dimeric architecture is discussed in terms of the stabilization and destabilization effects of the introduced mutations.

PubMed: 23519666
DOI: 10.1107/S0907444912051657

実験手法

X-RAY DIFFRACTION (2.26 Å)