Involvement of Phenylalanine 297 in the Construction of the Substrate Pocket of Human Aminopeptidase B

Biochemistry
Atsushi OhnishiMasafumi Tsujimoto

Abstract

Aminopeptidase B (APB, EC 3.4.11.6) preferentially hydrolyzes the N-terminal basic amino acids of synthetic and peptide substrates and requires a physiological concentration of NaCl for optimal activity. In this study, we used site-directed mutagenesis and molecular modeling to search for an amino acid residue that is critical for the enzymatic properties of human APB. Substitution of Phe297 with Tyr caused a significant decrease in hydrolytic activity toward synthetic and peptide substrates as well as chloride anion sensitivity. Molecular modeling suggests that Phe297 contributes to the construction of the substrate pocket of APB, which is wide enough to hold a chloride anion and allow the interaction of Gln169 with the N-terminal Arg residue of the substrate through bridging with the chloride anion. These results indicate that Phe297 is crucial for the optimal enzymatic activity and chloride anion sensitivity of APB via formation of the optimal structure of the catalytic pocket.

References

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May 26, 2007·The Journal of Biological Chemistry·Masato MaruyamaMasafumi Tsujimoto
Jan 15, 2014·Biochimica Et Biophysica Acta·Yuko OgawaMasafumi Tsujimoto
Nov 20, 2014·Protein Science : a Publication of the Protein Society·Stefan J HermansMichael W Parker

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Citations

Apr 3, 2020·Molecular and Cellular Biochemistry·Atsushi OhnishiMasafumi Tsujimoto
Mar 7, 2019·The Journal of Pharmacology and Experimental Therapeutics·Davin RautiolaRonald A Siegel
Feb 6, 2020·Biological & Pharmaceutical Bulletin·Masafumi TsujimotoYoshikuni Goto

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