Three-dimensional molecular modeling explains why catalytic function for angiotensin-I is different between human and rat chymases.

D Yamamoto; N Shiota; S Takai; T Ishida; H Okunishi; M Miyazaki

doi:10.1006/bbrc.1997.7875

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Three-dimensional molecular modeling explains why catalytic function for angiotensin-I is different between human and rat chymases.

D Yamamoto·N Shiota·S Takai·T Ishida·H Okunishi·M Miyazaki

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Abstract

Although angiotensin (ANG)-I is a substrate sensitive to chymase, the cleavage site differs among the chymase families. While human chymase (HC) hydrolyses the Phe8-His9 bond of ANG-I to ANG-II, rat chymase (RMCP-I) degrades the Tyr4-Ile5 bond of ANG-I to the inactive fragments. To clarify this different catalysis for ANG-I at the atomic level, three-dimensional structures of HC and RMCP-I were constructed by the molecular dynamic simulation. The energy-refined models clearly showed the significant difference in the electrostatic potential of the solvent surface. From the modeling study of their complex structures with ANG-I, the functional difference between both enzymes was clearly related with the electrostatic difference, especially at the C-terminal substrate-binding site.

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Amino Acid Sequence Angiotensin I Animals Binding Sites Chymases Computer Simulation Humans Models, Molecular Molecular Sequence Data Rats Sequence Homology, Amino Acid Serine Endopeptidases Species Specificity Substrate Specificity Comparative Study Journal Article Research Support, Non-U.S. Gov't

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D Yamamoto, N Shiota, S Takai, T Ishida, H Okunishi, M Miyazaki. 1998-01-06. Three-dimensional molecular modeling explains why catalytic function for angiotensin-I is different between human and rat chymases.. https://doi.org/10.1006/bbrc.1997.7875

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