3DFL

Crystal structure of human Prostasin complexed to 4-guanidinobenzoic acid

3DFL の概要

• エントリーDOI: 10.2210/pdb3dfl/pdb
• 関連するPDBエントリー: 3DFJ
• 分子名称: Prostasin, 4-carbamimidamidobenzoic acid (3 entities in total)
• 機能のキーワード: prostasin, serine protease, glycoprotein, hydrolase, membrane, secreted, transmembrane, zymogen
• 由来する生物種: Homo sapiens
• 細胞内の位置: Prostasin: Cell membrane; Single-pass membrane protein. Prostasin light chain: Secreted, extracellular space. Prostasin heavy chain: Secreted, extracellular space: Q16651
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28567.92

構造登録者

Su, H.P.,Rickert, K.W.,Darke, P.L.,Munshi, S.K. (登録日: 2008-06-12, 公開日: 2008-10-14, 最終更新日: 2024-10-30)

主引用文献

Rickert, K.W.,Kelley, P.,Byrne, N.J.,Diehl, R.E.,Hall, D.L.,Montalvo, A.M.,Reid, J.C.,Shipman, J.M.,Thomas, B.W.,Munshi, S.K.,Darke, P.L.,Su, H.P.
Structure of human prostasin, a target for the regulation of hypertension.
J.Biol.Chem., 283:34864-34872, 2008

PubMed Abstract: Prostasin (also called channel activating protease-1 (CAP1)) is an extracellular serine protease implicated in the modulation of fluid and electrolyte regulation via proteolysis of the epithelial sodium channel. Several disease states, particularly hypertension, can be affected by modulation of epithelial sodium channel activity. Thus, understanding the biochemical function of prostasin and developing specific agents to inhibit its activity could have a significant impact on a widespread disease. We report the expression of the prostasin proenzyme in Escherichia coli as insoluble inclusion bodies, refolding and activating via proteolytic removal of the N-terminal propeptide. The refolded and activated enzyme was shown to be pure and monomeric, with kinetic characteristics very similar to prostasin expressed from eukaryotic systems. Active prostasin was crystallized, and the structure was determined to 1.45 A resolution. These apoprotein crystals were soaked with nafamostat, allowing the structure of the inhibited acyl-enzyme intermediate structure to be determined to 2.0 A resolution. Comparison of the inhibited and apoprotein forms of prostasin suggest a mechanism of regulation through stabilization of a loop which interferes with substrate recognition.

PubMed: 18922802
DOI: 10.1074/jbc.M805262200

実験手法

X-RAY DIFFRACTION (2 Å)