Crystal structure of two quaternary complexes of dethiobiotin synthetase, enzyme-MgADP-AlF3-diaminopelargonic acid and enzyme-MgADP-dethiobiotin-phosphate; implications for catalysis

The crystal structures of two complexes of dethiobiotin synthetase, enzyme- diaminopelargonic acid-MgADP-AlF3 and enzyme-dethiobiotin-MgADP-Pi, respect ively, have been determined to 1.8 Angstrom resolution. In dethiobiotin syn thetase, AlF3 together with carbamylated diaminopelargonic acid mimics the phosphorylated reaction intermediate rather than the transition state compl ex for phosphoryl transfer. Observed differences in the binding of substrat e, diaminopelargonic acid, and the product, dethiobiotin, suggest considera ble displacements of substrate atoms during the ring closure step of the ca talytic reaction. In both complexes, two metal ions are observed at the act ive site, providing evidence for a two-metal mechanism for this enzyme.