Serine hydroxymethyltransferase (SHMT) is a pyridoxal 5’-phosphate (PLP)-dependent enzyme and a promising drug target, however, PLP-dependent catalysis remains underexplored. Here, the authors report joint X-ray/neutron structures of Thermus thermophilus SHMT in the internal aldimine state and in complex with L-serine substrate trapped at the peripheral binding site, revealing positions of hydrogen atoms, assigning the protonation states and electrical charges of residues, and proposing a catalytic mechanism.
- Victoria N. Drago
- Claudia Campos
- Andrey Kovalevsky
