1WZ9

The 2.1 A structure of a tumour suppressing serpin

1WZ9 の概要

• エントリーDOI: 10.2210/pdb1wz9/pdb
• 関連するPDBエントリー: 1XU8
• 分子名称: Maspin precursor, SULFATE ION (3 entities in total)
• 機能のキーワード: maspin, serpin, tumor suppressor, serpinb5, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space: P36952
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85362.02

構造登録者

Law, R.H.,Irving, J.A.,Buckle, A.M.,Ruzyla, K.,Buzza, M.,Bashtannyk-Puhalovich, T.A.,Beddoe, T.C.,Kim, N.,Worrall, D.M.,Bottomley, S.P.,Bird, P.I.,Rossjohn, J.,Whisstock, J.C. (登録日: 2005-03-03, 公開日: 2005-03-15, 最終更新日: 2024-10-30)

主引用文献

Law, R.H.,Irving, J.A.,Buckle, A.M.,Ruzyla, K.,Buzza, M.,Bashtannyk-Puhalovich, T.A.,Beddoe, T.C.,Nguyen, K.,Worrall, D.M.,Bottomley, S.P.,Bird, P.I.,Rossjohn, J.,Whisstock, J.C.
The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix.
J.Biol.Chem., 280:22356-22364, 2005

PubMed Abstract: Maspin is a serpin that acts as a tumor suppressor in a range of human cancers, including tumors of the breast and lung. Maspin is crucial for development, because homozygous loss of the gene is lethal; however, the precise physiological role of the molecule is unclear. To gain insight into the function of human maspin, we have determined its crystal structure in two similar, but non-isomorphous crystal forms, to 2.1- and 2.8-A resolution, respectively. The structure reveals that maspin adopts the native serpin fold in which the reactive center loop is expelled fully from the A beta-sheet, makes minimal contacts with the core of the molecule, and exhibits a high degree of flexibility. A buried salt bridge unique to maspin orthologues causes an unusual bulge in the region around the D and E alpha-helices, an area of the molecule demonstrated in other serpins to be important for cofactor recognition. Strikingly, the structural data reveal that maspin is able to undergo conformational change in and around the G alpha-helix, switching between an open and a closed form. This change dictates the electrostatic character of a putative cofactor binding surface and highlights this region as a likely determinant of maspin function. The high resolution crystal structure of maspin provides a detailed molecular framework to elucidate the mechanism of function of this important tumor suppressor.

PubMed: 15760906
DOI: 10.1074/jbc.M412043200

実験手法

X-RAY DIFFRACTION (2.1 Å)