Mechanistic consequences of charge transfer systems in serine proteases and angiotensin: semiempirical computations.
Structures and relative energies for the triads of interacting groups in the serine charge relay system of serine proteases and the proposed tyrosine charge relay system of angiotensin II, respectively, were computed according to the standard MNDOC procedure. The most stable configuration obtained for both systems was one in which the histidine residue was negatively charged. These findings indicate that the histidine ring and not the serine hydroxyl group at the active site of serine proteases would be the nucleophilic center which is acylated by substrate. Similarly, the extreme nucleophilicity of the imidazole anion produced by the proposed triad of interacting groups in angiotensin could provoke the formation of a transient covalent bond (acyl intermediate) between receptor and peptide in the receptor activation mechanism.
Rauk
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Hamilton
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Moore
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D000804:Angiotensin II / Q000378:metabolism*; D004355:Drug Stability; D010450:Endopeptidases / Q000378:metabolism*; D004795:Enzyme Stability; D011487:Protein Conformation; D012697:Serine Endopeptidases; D013816:Thermodynamics
D000804:Angiotensin II; D010450:Endopeptidases; D012697:Serine Endopeptidases