Work

Crystal structures of the phosphorylation mimics of human cytosolic branched chain aminotransferase

Year: 2025

Type: article

Abstract: The phosphorylation sites of the human cytosolic Branched Chain Aminotransferase (hBCATc) mediated by mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated-kinase 2 (ERK2, also known as MAPK1) were mapped. The crystal structures of the phosphorylation mimics at T33 and T36 were determined. The modified transaminase activity of these variants was analyzed. Although there were no major conformational changes in the phosphorylation mimics of hBCAT, a regional conformational change at the interdomain loop was observed mainly in mutant T33E. Consistently, when the catalytic turnovers of the T33E and T36E mutants were comparable to the wild type of hBCATc, the K M dropped significantly compared to the wild type, indicating a shift of the substrate binding affinity in the mutants. Taken together, this indicated the phosphorylation of hBCATc by ERK2 is affecting the hBCATc's transaminase activity.

Source: Archives of Biochemistry and Biophysics

DOI: 10.1016/j.abb.2025.110479

Authors: Elizabeth S. Dare, Robert H. Newman, Myra E. Conway, Ming Dong

Institutions: University of North Carolina Wilmington, North Carolina Agricultural and Technical State University, University of Derby

Language: English

Topic: Enzyme Structure and Function

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $3,170