Computer graphics modelling and the specificity of renins.

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Modeling

Background:

• Renins are aspartic proteinases crucial for blood pressure regulation.
• Understanding renin structure is key to developing targeted therapies.

Purpose of the Study:

• To model the three-dimensional structures of mouse submaxillary, mouse kidney, and human renins.
• To correlate structural features with renin specificity and function.

Main Methods:

• Utilized the high-resolution X-ray structure of endothiapepsin as a template.
• Incorporated amino acid sequences from protein, cDNA, and gene sequencing.
• Employed computer graphics for structural analysis.

Main Results:

• Renin models exhibit structures similar to other aspartic proteinases, with surface variations.
• Catalytically essential aspartates are located centrally within an extended active site cleft.
• Subsite differences, particularly at S3', correlate with known renin specificities.
• Surface residues near the active site may be involved in angiotensinogen binding.

Conclusions:

• Structural modeling provides insights into renin function and specificity.
• The findings support the role of specific residues in substrate recognition and binding.
• The models offer a basis for understanding renin's neutral pH optima.