1P8J

CRYSTAL STRUCTURE OF THE PROPROTEIN CONVERTASE FURIN

Summary for 1P8J

• Entry DOI: 10.2210/pdb1p8j/pdb
• Related PRD ID: PRD_000278
• Descriptor: 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)
• Functional Keywords: prohormone convertase, spc1, pace, p-domain, chloromethylketone, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 16
• Total formula weight: 426622.72

Authors

Henrich, S.,Cameron, A.,Bourenkov, G.P.,Kiefersauer, R.,Huber, R.,Lindberg, I.,Bode, W.,Than, M.E. (deposition date: 2003-05-07, release date: 2003-07-08, Last modification date: 2025-03-26)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)