3CWL

Crystal structure of alpha-1-antitrypsin, crystal form B

3CWL の概要

• エントリーDOI: 10.2210/pdb3cwl/pdb
• 関連するPDBエントリー: 3CWM
• 分子名称: Alpha-1-antitrypsin, CHLORIDE ION (3 entities in total)
• 機能のキーワード: antitrypsin, polymerisation, protein aggregation, protein unfolding, serpin, acute phase, disease mutation, glycoprotein, protease inhbitor, secreted, serine protease inhibitor, blood coagulation, protease inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted. Short peptide from AAT: Secreted, extracellular space, extracellular matrix: P01009
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44445.81

構造登録者

Morton, C.J.,Hansen, G.,Feil, S.C.,Adams, J.J.,Parker, M.W. (登録日: 2008-04-22, 公開日: 2008-09-23, 最終更新日: 2024-10-30)

主引用文献

Pearce, M.C.,Morton, C.J.,Feil, S.C.,Hansen, G.,Adams, J.J.,Parker, M.W.,Bottomley, S.P.
Preventing serpin aggregation: The molecular mechanism of citrate action upon antitrypsin unfolding.
Protein Sci., 17:2127-2133, 2008

PubMed Abstract: The aggregation of antitrypsin into polymers is one of the causes of neonatal hepatitis, cirrhosis, and emphysema. A similar reaction resulting in disease can occur in other human serpins, and collectively they are known as the serpinopathies. One possible therapeutic strategy involves inhibiting the conformational changes involved in antitrypsin aggregation. The citrate ion has previously been shown to prevent antitrypsin aggregation and maintain the protein in an active conformation; its mechanism of action, however, is unknown. Here we demonstrate that the citrate ion prevents the initial misfolding of the native state to a polymerogenic intermediate in a concentration-dependent manner. Furthermore, we have solved the crystal structure of citrate bound to antitrypsin and show that a single citrate molecule binds in a pocket between the A and B beta-sheets, a region known to be important in maintaining antitrypsin stability.

PubMed: 18780818
DOI: 10.1110/ps.037234.108

実験手法

X-RAY DIFFRACTION (2.44 Å)