Hypertension, Vol 7, 3-12, Copyright © 1985 by American Heart Association
K Akahane, H Umeyama, S Nakagawa, I Moriguchi, S Hirose, K Iizuka and K Murakami
A three-dimensional model of human renin has been constructed based on the
assumption that the overall folding of the aspartyl proteases is very
similar. As a reference, we used penicillopepsin, the structure of which
has been reported at a resolution of 1.8 A, and its main chain was traced
to build a model of renin. The resulting structure seems to be stable from
the hydrophobic and hydrophilic viewpoints. Comparison of the tertiary
structure of human renin with that of penicillopepsin and mouse renin
suggests the existence of a high structural homology as well as differences
in the molecular geometry of the active sites that may influence the
substrate specificity. The asparagine side chains in the glycosidation
signal of Asn-X-Thr are exposed on the surface. Moreover, the site in human
renin that corresponds to the proteolytic cleavage site in mouse renin also
appears to be exposed on the surface so as to be easily scissored during
the maturation process. The insertions and deletions of amino acid residues
were found to arise on the surface, and in some places they occurred in
complementary manners. Models of molecular complexes between human renin
and renin inhibitor were constructed to understand the interacting modes
that indicate how new renin inhibitors develop. Inhibitor-binding sites
were directly assigned based on the models of the inhibitor-enzyme complex.
ARTICLES
Three-dimensional structure of human renin
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