Key result
Substitutions of Phe, Ala, and His for Tyr83 of human renin reduced kcat at pH 6.5 to 11.1%, 1.31%, and 3.49% of wild-type renin, respectively, and eliminated the activity peak at pH 8.7.
Why the study?
Does substitution of Tyr83 in human renin alter the pH dependence and catalytic activity of the renin-angiotensinogen reaction?
Does substitution of Tyr83 in human renin alter the pH dependence and catalytic activity of the renin-angiotensinogen reaction?
Tyrosine-83 is essential for the catalytic reaction of human renin with angiotensinogen, particularly at basic pH.
Tyr83 is critical for renin catalysis; leaves open relevance to human hypertension or inhibitor design.
The pH dependence of the reaction of human renin with sheep angiotensinogen had a couple of peaks at pH 6.5 and 8.7. The renin activity at pH 8.7 was 1.4 times higher than that at pH 6.5. After the substitutions of Phe, Ala, and His for Tyr83 of human renin, the peak at pH 6.5 could be observed but the peak at pH 8.7 disappeared. At pH 6.5, these substitutions reduced the kcat of human renin to 11.1, 1.31, and 3.49% of that of wild-type renin, respectively, while their Km remained at similar levels to that of the wild type. These results indicate that Tyr83 of human renin contributes to the renin-angiotensinogen reaction at both pHs and it is essential for the catalytic reaction particularly at the basic pH.
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Nasir et al. (1999) studied this question. Substitutions of Phe, Ala, and His for Tyr83 of human renin vs. Wild-type human renin was evaluated on kcat and Km of human renin at pH 6.5 and 8.7. Substitutions of Phe, Ala, and His for Tyr83 of human renin reduced kcat at pH 6.5 to 11.1%, 1.31%, and 3.49% of wild-type renin, respectively, and eliminated the activity peak at pH 8.7.
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