Rabbit and Human Angiotensin-Converting Enzyme-2: Structure and Electric Properties

Area of Science:

• Biochemistry and Structural Biology
• Molecular Modeling and Bioinformatics

Background:

• Angiotensin-converting enzyme-2 (ACE2) is crucial for blood pressure regulation, converting vasoconstrictors to vasodilators.
• ACE2 gained prominence during the COVID-19 pandemic as the SARS-CoV-2 S-protein receptor.
• Understanding ACE2 structure-function relationships is vital for both physiological and pathological contexts.

Purpose of the Study:

• To reconstruct the 3D structure of the rabbit ACE2 (rACE2) catalytic domain from its amino acid sequence.
• To compare the structural, electric, and thermodynamic properties of rACE2 with human ACE2 (hACE2).
• To evaluate the suitability of rabbits as an animal model for human ACE2-related research.

Main Methods:

• Primary amino acid sequence analysis to reconstruct the 3D structure of rACE2.
• Computational protein electrostatics to calculate electric properties and thermodynamic stability.
• 3D alignment and comparison of rACE2 and hACE2 catalytic domains.

Main Results:

• High sequence identity (85%) between rACE2 and hACE2 polypeptide chains.
• Similarities in α-helix segments and minor differences in unstructured regions between the 3D structures.
• Coincident isoelectric points (pI 5.21) and comparable surface electrostatic potential distribution, despite charge differences.
• Maximal thermodynamic stability for both enzymes observed at pH 6.5, with pH-dependent electrostatic behavior.

Conclusions:

• Rabbit ACE2 exhibits significant structural and physicochemical similarity to human ACE2.
• The findings support the use of rabbits as a valid animal model for studying ACE2 functions.
• Results suggest extrapolating findings from rabbit ACE2 studies to human physiology and disease, including coronavirus infections.