Construction of a model for the three-dimensional structure of human renal renin.
The aspartyl proteases that have had their complete three-dimensional structures determined by x-ray diffraction techniques exhibit a high degree of structural homology and a correspondingly high degree of sequence homology. Using this homology, we constructed a model for the three-dimensional structure of human renal renin. We then refined and evaluated the model with the energy refinement program called CHARMM. We found that the model for human renin differs from that of mouse submaxillary gland renin in certain features, which may account for the differences in substrate specificity and antibody binding. Amino acid differences between human and mouse renin in the regions that bind the P1' side chain of the substrate appear to change only the shape of the S1' subsite of the enzyme, so that either valine or leucine side chains of the substrate can be accommodated by human renin. Amino acids in the solvent-accessible surface of the 75-85 flap appear to be distinctly different between the two structures and could account for the differences observed in antibody binding to human and mouse renin.
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000032:analysis; D001665:Binding Sites; D006801:Humans; D007668:Kidney / Q000032:analysis*; D051379:Mice; D011487:Protein Conformation; D012083:Renin
D001224:Aspartic Acid; D012083:Renin