April 26, 2023

The Banerjee lab publishes a research article in PNAS

Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair

Overlay of MCM•cob(II)alamin•ADP (dark gray), MCM•AdoCbl•malonyl-CoA (PDB 2XIQ, light gray) and MCM•OH2Cbl (pink). The adenine moieties in ADP (blue) and AdoCbl (gray) overlay, while the diphosphate of ADP overlays on the corresponding moiety in malonyl-CoA (purple).

Human methylmalonyl-coenzyme A (CoA) mutase (MCM) catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA using the high-value metallocofactor 5′-deoxyadenosylcobalamin (AdoCbl). In this study, researchers in the Banerjee lab report the unexpected discovery that ADP functions as a bivalent mimic of the AdoCbl cofactor and the methylmalonyl-CoA substrate of MCM to protect cob(II)alamin from hyperoxidation and promote its repair. The authors of the new publication are graduate student Harsha Gouda, postdoctoral fellow Romila Mascarenhas, research investigator Markus Ruetz, research associate Madeline Yaw, and professor Ruma Banerjee.

Research article in PNAS