High molecular weight transglutaminase inhibitor produced by a microorganism (Streptomyces lavendulae Y-200).
Transglutaminases catalyze the cross-linking and amine incorporation of proteins, and are implicated in various biological phenomena such as blood clotting, wound healing, apoptosis, and cell differentiation. Streptomyces lavendulae Y-200, isolated from soil, produced a substance that inhibited transglutaminases. The inhibitory substance was purified from the cultured medium by procedures of acid precipitation, deoxyribonuclease treatment, and gel filtration chromatography. The partially purified sample was dark brown. The inhibitory activity was stable under acidic, alkaline, and high temperature conditions, and resistant to the treatment with proteinases such as trypsin and Pronase. The molecular weight of the inhibitory substance was estimated to be between 10(4) and 10(5) from its permeability through ultrafilter membranes. The acid hydrolysate of the inhibitory substance contained amino acids and sugars. The inhibitory substance inhibited both calcium-dependent and calcium-independent transglutaminases in a competitive manner with a glutamine substrate. The extent of inhibition caused by the calcium-dependent transglutaminase increased with increasing calcium concentration. The results obtained here may help identify a novel regulatory substance of transglutaminase in biological systems.
Ikura
K
K
Department of Applied Biology, Kyoto Institute of Technology, Japan. ikura@ipc.kit.ac.jp
Minami
K
K
Otomo
C
C
Hashimoto
H
H
Natsuka
S
S
Oda
K
K
Nakanishi
K
K
D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D002384:Catalysis; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification*; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D006358:Hot Temperature; D008970:Molecular Weight; D011402:Pronase / Q000378:metabolism; D013302:Streptomyces / Q000737:chemistry*; D011503:Transglutaminases / Q000037:antagonists & inhibitors*; D014357:Trypsin / Q000378:metabolism; D014462:Ultrafiltration
D002364:Caseins; D004791:Enzyme Inhibitors; C002087:N,N-dimethylcasein; D006632:Histamine; D011503:Transglutaminases; D014357:Trypsin; D011402:Pronase; D002118:Calcium