A conceptual model of the polyamine binding site of N1-acetylpolyamine oxidase developed from a study of polyamine derivatives.
We used various polyamine derivatives to study the substrate binding site of N1-acetylpolyamine oxidase (PAO) that was partially purified from rat liver. The substrate activities of acetylpolyamines indicated the presence of two anionic centers corresponding to the 1,3-diaminopropane (1,3-DAP) structure and a hydrophobic region in addition to the cleavage site of the acetamidopropyl group. Based on the results of the inhibitory activities of 1,3-DAP derivatives, we developed a conceptual model of the polyamine binding site of PAO. We used this model to identify a potent competitive inhibitor, N1,N7-dihexyl-1,7-diamino-4-azaheptane, and to develop an affinity column, 1,16-diamino4,13-diazahexadecane-linked Sepharose, which was useful for the purification of PAO.
Takao
Koichi
K
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan. ktakao@josai.ac.jp
Shibata
Satoko
S
Ozawa
Tomohiro
T
Wada
Makiko
M
Sugitia
Yoshiaki
Y
Samejima
Keijiro
K
Shirahata
Akira
A
D000818:Animals; D001665:Binding Sites; D008958:Models, Molecular; D015394:Molecular Structure; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry* / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D011073:Polyamines; D000587:Oxidoreductases Acting on CH-NH Group Donors; C545272:N(1)-acetylpolyamine oxidase, rat