4MYD
1.37 Angstrom Crystal Structure of E. Coli 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (MenH) in complex with SHCHC
Summary for 4MYD
| Entry DOI | 10.2210/pdb4myd/pdb |
| Related | 4MXD 4MYS |
| Descriptor | 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase, 2-(3-CARBOXYPROPIONYL)-6-HYDROXY-CYCLOHEXA-2,4-DIENE CARBOXYLIC ACID (3 entities in total) |
| Functional Keywords | alpha/beta hydrolase fold, 2-succinyl-6-hydroxy-2, 4-cyclohexadiene-1-carboxylate synthase, lyase |
| Biological source | Escherichia coli |
| Total number of polymer chains | 3 |
| Total formula weight | 83620.43 |
| Authors | |
| Primary citation | Sun, Y.,Yin, S.,Feng, Y.,Li, J.,Zhou, J.,Liu, C.,Zhu, G.,Guo, Z. Molecular basis of the general base catalysis of an alpha / beta-hydrolase catalytic triad. J.Biol.Chem., 289:15867-15879, 2014 Cited by PubMed Abstract: The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to being a specific general base by an open-closed conformational change in the catalysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical α/β-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of half of the α-helical cap domain, which causes extensive structural changes in the α/β-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche conformation to form the functional triad. NMR analysis shows that the inactive open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couples formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the nucleophilicity of the triad, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis. PubMed: 24737327DOI: 10.1074/jbc.M113.535641 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.374 Å) |
Structure validation
Download full validation report
