title: PLP undergoes conformational changes during the course of an enzymatic reaction.
abstract: 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.
authors: Department of Biological Sciences, Konkuk University, 1 Hwayang dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors: Ho-Phuong-Thuy
authors: HP
authors: Ngo
authors: Center for Cellular and Structural Biology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors: Nuno M F S A
authors: NM
authors: Cerqueira
authors: Department of Biological Sciences, Konkuk University, 1 Hwayang dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors: Jin-Kwang
authors: JK
authors: Kim
authors: Department of Biological Sciences, Konkuk University, 1 Hwayang dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors: Myoung-Ki
authors: MK
authors: Hong
authors: Requimte/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
authors: Pedro Alexandrino
authors: PA
authors: Fernandes
authors: Requimte/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
authors: Maria João
authors: MJ
authors: Ramos
authors: Department of Biological Sciences, Konkuk University, 1 Hwayang dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors: Lin-Woo
authors: LW
authors: Kang
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D007700:Kinetics; D012695:L-Serine Dehydratase / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011732:Pyridoxal Phosphate / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012545:Schiff Bases; D013379:Substrate Specificity; D014974:Xanthomonas / Q000737:chemistry* / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D012545:Schiff Bases; D011732:Pyridoxal Phosphate; D012695:L-Serine Dehydratase
keywords: PLP-dependent enzymes; Xanthomonas oryzae pv. oryzae; XometC; cofactor conformational change; cofactor-based catalysis; pyridoxal 5′-phosphate