PMID:16023668
| Citation |
Vainer, R, Belakhov, V, Rabkin, E, Baasov, T and Adir, N (2005) Crystal structures of Escherichia coli KDO8P synthase complexes reveal the source of catalytic irreversibility. J. Mol. Biol. 351:641-52 |
|---|---|
| Abstract |
The enzyme 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase (KDO8PS) catalyses the condensation of arabinose 5-phosphate (A5P) and phosphoenol pyruvate (PEP) to obtain 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P). We have elucidated initial modes of ligand binding in KDO8PS binary complexes by X-ray crystallography. Structures of the apo-enzyme and of binary complexes with the substrate PEP, the product KDO8P and the catalytically inactive 1-deoxy analog of arabinose 5-phosphate (1dA5P) were obtained. The KDO8PS active site resembles an irregular funnel with positive electrostatic potential situated at the bottom of the PEP-binding sub-site, which is the primary attractive force towards negatively charged phosphate moieties of all ligands. The structures of the ligand-free apo-KDO8PS and the binary complex with the product KDO8P visualize for the first time the role of His202 as an active-site gate. Examination of the crystal structures of KDO8PS with the KDO8P or 1dA5P shows these ligands bound to the enzyme in the PEP-binding sub-site, and not as expected to the A5P sub-site. Taken together, the structures presented here strengthen earlier evidence that this enzyme functions predominantly through positional catalysis, map out the roles of active-site residues and provide evidence that explains the total lack of catalytic reversibility. |
| Links |
PubMed Online version:10.1016/j.jmb.2005.06.021 |
| Keywords |
Aldehyde-Lyases/chemistry; Aldehyde-Lyases/metabolism; Binding Sites; Catalysis; Crystallography, X-Ray; Escherichia coli/enzymology; Models, Molecular; Static Electricity |
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