Production of angiotensin-converting enzyme inhibitors from baker's yeast glyceraldehyde-3-phosphate dehydrogenase.
Angiotensin-converting enzyme (ACE) inhibitors were excised from the molecule of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of baker's yeast by heating at 120 degrees C in 1 M AcOH-20 mM HCl. Three inhibitors were then purified by gel-permeation and reverse-phase chromatographies. One of the yeast ACE inhibitors, YG-3, was GAPDH peptide 79-89 (Pro-Ala-Asn-Leu-Pro-Trp-Gly-Ser-Ser-Asn-Val, IC50:18 microM), and contained the sequence homologous to vertebrate ACE inhibitors (GAPDH peptides 79-86 or 81-88). Other inhibitors, YG-1 (Gly-His-Lys-Ile-Ala-Thr-Phe-Gln-Glu-Arg, IC50: 0.4 microM) and YG-2 (Gly-Lys-Lys-Ile-Ala-Thr-Tyr-Gln-Glu-Arg, IC50: 2 microM), corresponded to amino acid residues 68-77 in two different forms of yeast GAPDH, respectively. Their sequences were quite different from those of the venom peptide family. YG-1 was the most potent ACE inhibitor among yeast and vertebrate GAPDH peptides excised by acid-limited proteolysis. Thus, yeast GAPDH seems to be an excellent source of naturally occurring ACE inhibitors.
Kohama
Y
Y
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Nagase
Y
Y
Oka
H
H
Nakagawa
T
T
Teramoto
T
T
Murayama
N
N
Tsujibo
H
H
Inamori
Y
Y
Mimura
T
T
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases