Download citation
Download citation
link to html
Numerous enzymes, such as the pyridoxal 5'-phosphate (PLP)-dependent enzymes, require cofactors for their activities. Using X-ray crystallography, structural snapshots of the L-­serine dehydratase catalytic reaction of a bacterial PLP-dependent enzyme were determined. In the structures, the dihedral angle between the pyridine ring and the Schiff-base linkage of PLP varied from 18° to 52°. It is proposed that the organic cofactor PLP directly catalyzes reactions by active conformational changes, and the novel catalytic mechanism involving the PLP cofactor was confirmed by high-level quantum-mechanical calculations. The conformational change was essential for nucleophilic attack of the substrate on PLP, for concerted proton transfer from the substrate to the protein and for directing carbanion formation of the substrate. Over the whole catalytic cycle, the organic cofactor catalyzes a series of reactions, like the enzyme. The conformational change of the PLP cofactor in catalysis serves as a starting point for identifying the previously unknown catalytic roles of organic cofactors.

Supporting information

pdf

Portable Document Format (PDF) file https://doi.org/10.1107/S1399004713031283/dw5070sup1.pdf
Supporting Information.

avi

AVI file https://doi.org/10.1107/S1399004713031283/dw5070sup2.avi
The proposed mechanism of L-serine dehydratase activity by XometC. The full catalytic cycle is represented based on the intermediate structures. The conformations of PLP and active-site residues are taken from crystallographic intermediate structures in order to explain the catalytic mechanism in detail. Nucleophilic attack and electron transfer are shown as red arrows.

PDB references: XometC, native, 4ixz; EAS and EAA, 4iy7; PGD, EAA and IAI, 4iyo


Follow Acta Cryst. D
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds