Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase as a source of angiotensin-converting enzyme inhibitors.
The more potent inhibitory activity against angiotensin-converting enzyme (ACE) was excised from a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of Bacillus stearothermophilus by heating at 120 degrees C in 1 M AcOH-20 mM HCl, as compared with GAPDH preparations of yeast and pig. Sufficient excision of B. stearothermophilus ACE inhibitors required a longer proteolysis time of 60 min. Two inhibitors were then purified by gel-permeation and reverse-phase chromatographies. One of the B. stearothermophilus ACE inhibitors BG-1, was the GAPDH peptide 68-77 (Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg, IC50: 32 microM). Another inhibitor, BG-2 (Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr, IC50: 6 microM), correspond to GAPDH peptide 304-313. These sequences were quite different from those of vertebrate GAPDH peptides and the venom peptide family with ACE inhibitory activity. BG-2 was found to be a non-competitive type inhibitor, differing from many natural peptide inhibitors. Thus, B. stearothermophilus GAPDH seemed to be a good source of new type ACE inhibitors, in addition to the advantages due to its thermophilic property.
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Y
Y
Kohama
T
T
Nakagawa
H
H
Oka
Y
Y
Okuno
T
T
Mimura
H
H
Tsujibo
Y
Y
Inamori
R
R
Tsurutani
K
K
Nagata
K
K
Tomita
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism*; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D001411:Geobacillus stearothermophilus / Q000201:enzymology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000032:analysis; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology; D017967:Zinc Compounds
D000806:Angiotensin-Converting Enzyme Inhibitors; D002712:Chlorides; D010446:Peptide Fragments; D010455:Peptides; D017967:Zinc Compounds; C068142:glyceraldehyde 3-phosphate dehydrogenase (304-313); D012710:Serum Albumin, Bovine; C016837:zinc chloride; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D015032:Zinc