Creatine is an essential component for the temporal and spatial maintenance of the energy supply to skeletal and cardiac muscles. Creatine transporter protein (CRT) encoded by X-linked gene SLC6A8 helps transporting creatine from outside of skeletal and cardiac cells to inside the cells. Deficiency of creatine is found to be associated with creatine deficiency syndrome (CDS) in inborn characterized by clinical features like mental retardation, hypotonia, seizures, behavioral problem, speech delay etc. Here we focus on revealing the pathway of creatine through the CRT via steered molecular dynamics (MD) simulations. We show that creatine follows well-defined pathway despite of the choice of initial CRT structure and creatine position. The role of Na<sup>+ </sup>is also investigated and it was found that they affect creatine transport. Furthermore, we use the residues involved in creatine pathway to explain the molecular mechanism of known pathogenic mutations.

Revealing creatine pathway across creatine transporter protein

ACS Spring Meeting 2021

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