1P8J

CRYSTAL STRUCTURE OF THE PROPROTEIN CONVERTASE FURIN

1P8J の概要

• エントリーDOI: 10.2210/pdb1p8j/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000278
• 分子名称: Furin precursor, DECANOYL-ARG-VAL-LYS-ARG-CHLOROMETHYLKETONE INHIBITOR, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: prohormone convertase, spc1, pace, p-domain, chloromethylketone, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 426622.72

構造登録者

Henrich, S.,Cameron, A.,Bourenkov, G.P.,Kiefersauer, R.,Huber, R.,Lindberg, I.,Bode, W.,Than, M.E. (登録日: 2003-05-07, 公開日: 2003-07-08, 最終更新日: 2025-03-26)

主引用文献

Henrich, S.,Cameron, A.,Bourenkov, G.P.,Kiefersauer, R.,Huber, R.,Lindberg, I.,Bode, W.,Than, M.E.
The Crystal Structure of the Proprotein Processing Proteinase Furin Explains its Stringent Specificity
Nat.Struct.Biol., 10:520-526, 2003

PubMed Abstract: In eukaryotes, many essential secreted proteins and peptide hormones are excised from larger precursors by members of a class of calcium-dependent endoproteinases, the prohormone-proprotein convertases (PCs). Furin, the best-characterized member of the mammalian PC family, has essential functions in embryogenesis and homeostasis but is also implicated in various pathologies such as tumor metastasis, neurodegeneration and various bacterial and viral diseases caused by such pathogens as anthrax and pathogenic Ebola virus strains. Furin cleaves protein precursors with narrow specificity following basic Arg-Xaa-Lys/Arg-Arg-like motifs. The 2.6 A crystal structure of the decanoyl-Arg-Val-Lys-Arg-chloromethylketone (dec-RVKR-cmk)-inhibited mouse furin ectodomain, the first PC structure, reveals an eight-stranded jelly-roll P domain associated with the catalytic domain. Contoured surface loops shape the active site by cleft, thus explaining furin's stringent requirement for arginine at P1 and P4, and lysine at P2 sites by highly charge-complementary pockets. The structure also explains furin's preference for basic residues at P3, P5 and P6 sites. This structure will aid in the rational design of antiviral and antibacterial drugs.

PubMed: 12794637
DOI: 10.1038/nsb941

実験手法

X-RAY DIFFRACTION (2.6 Å)