Yasemin Ocak1, & Jason O. Matos2, 1Ridge High School, Basking Ridge, New Jersey, USA, 2Institute for Plant-Human Interface, Northeastern University, Boston, MA 02120, USA
Serotonin is an important neurotransmitter in learning, memory, happiness, as well as regulating homeostasis. Abnormal levels of serotonin can result in disorders such as depression, OCD, PTSD, schizophrenia, and serotonin syndrome. Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in the production of serotonin. Mutations in TPH2 can result in the disorders discussed above. Thus, TPH2 is a major drug target. TPH2 functions as a homotetramer in the cell, and consists of catalytic, regulatory, and oligomeric domains. Details of how these domains interact are lacking. Structural insight into TPH2 could help find molecules that regulate its activity. While we do know the structures of the domains separately, we don’t know exactly how they interact. In order to determine how these domains interact, the new technology AlphaFold 3 was used. While AlphaFold 3 is said to have transformed the field of structural biology, in this study we will test whether AlphaFold predictions are accurate by proposing mutants of TPH2 that are at the interface of the regulatory and catalytic domains. Taken together, our ef orts will be able to determine if the structure predicted by AlphaFold for a multi- domain protein is accurate.
Serotonin, Tryptophan hydroxylase 2 (TPH2), AlphaFold 3, Depression, OCD, PTSD, Serotonin syndrome, Homotetramer, Catalytic domain, Regulatory domain, Domain interactions, Structural biology, Drug target, Protein structure prediction, TPH2 mutations.
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