Chat GPT Q&A, page-119

the significance of the interaction between the N-terminal and C-terminal domains of the FTO protein and how this interaction is relevant to the function of FTO and its potential as a target for drug development. Here's what the comments say:

1. The N-terminal domain of FTO is important for its catalytic function (catalyzing demethylation of N6-methyladenosine). However, this domain is unstable when separated from the C-terminal domain.

2. The instability of the N-terminal domain when isolated explains why it is not competent for catalysis. In other words, both the N-terminal and C-terminal domains of FTO need to interact for FTO to perform its enzymatic function.

3. This interaction between the domains is considered a target for the development of specific inhibitors. Inhibiting this interaction could potentially interfere with FTO's function, making it a target for drugs designed to treat conditions associated with FTO overexpression, such as obesity and cancer.

4. The passage also mentions that advanced techniques like NMR (Nuclear Magnetic Resonance) were used to study the structural dynamics of FTO, showing that the interface between the structural domains and the active site undergo conformational changes on various timescales.

5. The structural ensemble obtained in this study provides a detailed atomic-resolution model of FTO, and it reveals areas at the domain interface that could be potential targets for the design of allosteric inhibitors. This means that understanding the interaction between the domains can help identify specific sites on FTO where drugs can be designed to modulate its activity.