Active prorenin: evidence for the formation of a conformational variant of recombinant human prorenin.
Using highly purified recombinant human prorenin, we report the first evidence for the formation of a stable, partially active, conformational variant of the recombinant proenzyme. The enzymatically active prorenin exhibits the following characteristics: (1) the proenzyme N-terminal sequence and molecular weight are maintained; (2) the active proenzyme is capable of cleaving a novel fluorogenic peptide substrate based on the sequence of human angiotensinogen and exhibits about 30% of mature renin specific activity for the fluorogenic substrate; (3) the active proenzyme conformation binds to, and can be eluted from, a pepstatin affinity column; and (4) the activity of the active proenzyme can be inhibited by a novel peptidomimetic renin inhibitor.
Edalji
R
R
Protein Biochemistry, Pharmaceutical Discovery Research, Abbott Laboratories, Abbott Park, Illinois 60064.
Holzman
T F
TF
Gubbins
E J
EJ
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004151:Dipeptides; D004792:Enzyme Precursors / Q000737:chemistry*; D005470:Fluorometry; D006801:Humans; D008969:Molecular Sequence Data; D010436:Pepstatins / Q000737:chemistry; D011487:Protein Conformation; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000737:chemistry; D012083:Renin / Q000737:chemistry*; D000092502:Renin Inhibitors
D004151:Dipeptides; D004792:Enzyme Precursors; D010436:Pepstatins; D011994:Recombinant Proteins; D012083:Renin; D000092502:Renin Inhibitors; C056622:enalkiren; C014195:Streptomyces pepsin inhibitor; C031375:pepstatin