PMID- 7819325
OWN - NLM
STAT- MEDLINE
DCOM- 19950216
LR  - 20190821
IS  - 0300-9084 (Print)
IS  - 0300-9084 (Linking)
VI  - 76
IP  - 3-4
DP  - 1994
TI  - Furin-mediated proprotein processing activity: involvement of negatively charged 
      amino acid residues in the substrate binding region.
PG  - 210-6
AB  - Furin, which is encoded by the recently discovered FUR gene, appears to be the 
      first known mammalian member of the subtilisin family of serine proteases with 
      cleavage selectivity for paired or multiple basic residues. A consensus cleavage 
      sequence, Arg-X-Lys/Arg-Arg has been proposed. Most likely, furin is primarily 
      involved in the processing of precursors of proteins that are secreted via the 
      constitutive secretory pathway. Homology modelling of the catalytic domain of 
      this protein suggested that negatively charged amino acid residues near or in the 
      substrate binding region might contribute to the observed specificity for 
      substrate segments with paired and multiple basic amino acid residues. To 
      investigate this hypothesis, furin mutants were generated in which negatively 
      charged residues, predicted to be located near or in the substrate binding 
      pockets and involved in interactions with basic residues of the substrate, were 
      replaced by neutral residues. Analysis of processing by these furin mutants of 
      wild-type and cleavage mutants of pro-von Willebrand factor (pro-vWF) revealed 
      that particular negatively charged residues are critical for specific cleavage 
      activity.
FAU - Roebroek, A J
AU  - Roebroek AJ
AD  - Laboratory for Molecular Oncology, University of Leuven, Belgium.
FAU - Creemers, J W
AU  - Creemers JW
FAU - Ayoubi, T A
AU  - Ayoubi TA
FAU - Van de Ven, W J
AU  - Van de Ven WJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - EC 3.4.21.- (Subtilisins)
RN  - EC 3.4.21.75 (Furin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Conserved Sequence
MH  - Furin
MH  - Humans
MH  - Mammals
MH  - *Protein Processing, Post-Translational
MH  - Protein Structure, Secondary
MH  - Subtilisins/*chemistry/genetics/*metabolism
RF  - 50
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
AID - 0300-9084(94)90148-1 [pii]
AID - 10.1016/0300-9084(94)90148-1 [doi]
PST - ppublish
SO  - Biochimie. 1994;76(3-4):210-6. doi: 10.1016/0300-9084(94)90148-1.