Effects of substitution of Val for Leu11 of ovine angiotensinogen on renin activity.
A mutant angiotensinogen, L11V, in which Val11 was substituted for Leu11 of ovine angiotensinogen was prepared to have the same scissile peptide bond as the human one. The mutation didn't vary Km and kcat of human renin for the ovine substrate, but decreased those of rat renin to one half and one fortieth, respectively. Distances between the P1' subsite of angiotensinogens and the 224th (human renin numbering) residue in the S1' subsite of renins were estimated by molecular modelings. The marked decrease in kcat of rat renin for L11V could be attributed to the elongated distance between Val11 of L11V and Val221 of rat renin. It was also suggested that the distance is the reason why the human substrate cannot be cleaved by heterologous renins.
Inui
Y
Y
United Graduate School of Agricultural Science, Gifu University, Japan.
Orihashi
T
T
Okada
E
E
Nakagawa
T
T
Ebihara
A
A
Suzuki
F
F
Nakamura
Y
Y
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000737:chemistry*; D000818:Animals; D001483:Base Sequence; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D012083:Renin / Q000737:chemistry*; D012756:Sheep; D013045:Species Specificity; D014633:Valine / Q000737:chemistry*