Lapstatin, a new aminopeptidase inhibitor produced by Streptomyces rimosus, inhibits autogenous aminopeptidases.
Lapstatin, a low-molecular-weight aminopeptidase inhibitor, was purified to homogeneity from Streptomyces rimosus culture filtrates. The purification procedure included extraction with methanol, followed by chromatography on Dowex 50WX4, AG50WX4, and HPLC RP C18 columns. By amino acid analysis, mass spectrometry, and NMR spectroscopy, the structure of lapstatin was shown to be 3-amino-2-hydroxy-4-methylpentanoylvaline. Lapstatin inhibited the extracellular leucine aminopeptidases from Streptomyces rimosus, Streptomyces griseus, and Aeromonas proteolytica with an IC50 in the range of 0.3-2.4 microM. IC50 values for other enzymes tested were at least tenfold higher. Leucine aminopeptidase from Streptomyces griseus was inhibited in a competitive manner, with an inhibition constant of 5 x 10(-7) M. Lapstatin is the first low-molecular-weight compound isolated from streptomycetes shown to inhibit an autogenous aminopeptidase.
Repic Lampret
B
B
Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, Jamova 39, 1000 Ljubljana, Slovenia. barbka.repic@ijs.si
Kidric
J
J
Kralj
B
B
Vitale
L
L
Pokorny
M
M
Renko
M
M
D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013302:Streptomyces / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C120110:lapstatin; D007931:Leucyl Aminopeptidase; D014633:Valine