Functional characterization of Narc 1, a novel proteinase related to proteinase K.
The NARC 1 gene encodes a novel proteinase K family proteinase. The domain structure of rat Narc 1 resembles that of the subtilisin-like proprotein convertases (SPCs), except that rNarc 1 lacks the canonical P-domain of SPCs, retaining only the RGD motif as part of what might be a cryptically functioning P-domain. Narc 1 undergoes autocatalytic intramolecular processing at the site LVFAQ/, resulting in the cleavage of its prosegment and the generation of an active proteinase with a broad alkaline pH optimum and no apparent calcium requirement for activity. Both primary and secondary structural determinants influence Narc 1 substrate recognition. Our functional characterization of Narc 1 reinforces the inference drawn from the analysis of its predicted structure that this enzyme is most closely related to representatives of the proteinase K family, but that it is also sufficiently different to warrant its possible classification in a separate sub-family.
Naureckiene
Saule
S
Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA.
Ma
Linh
L
Sreekumar
Kodangattil
K
Purandare
Urmila
U
Lo
C Frederick
CF
Huang
Ying
Y
Chiang
Lillian W
LW
Grenier
Jill M
JM
Ozenberger
Bradley A
BA
Jacobsen
J Steven
JS
Kennedy
Jeffrey D
JD
DiStefano
Peter S
PS
Wood
Andrew
A
Bingham
Brendan
B
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000737:chemistry; D019286:Endopeptidase K / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D004795:Enzyme Stability; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D000071449:Proprotein Convertase 9; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D017385:Sequence Homology; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013696:Temperature
D009842:Oligopeptides; D011994:Recombinant Proteins; C047981:arginyl-glycyl-aspartic acid; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D012697:Serine Endopeptidases; D019286:Endopeptidase K; D002118:Calcium