Structural and thermodynamical insights into the binding and inhibition of FIH-1 by the N-terminal disordered region of Mint3.

ABSTRACT: Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which makes investigation of this interaction challenging. Therefore, we adopted thermodynamic and structural studies in solution to clarify the structural and thermodynamical changes of Mint3 binding to FIH-1. First, using a combination of circular dichroism, nuclear magnetic resonance, and hydrogen/deuterium exchange-mass spectrometry (HDX-MS), we confirmed that the N-terminal half, which is the interacting part of Mint3, is mostly disordered. Next, w

SUBMITTER: Ten T 

PROVIDER: S-EPMC8571082 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature