3EL6: Crystal Structure of the Erythromycin Dehydratase

The dehydratases (DHs) of modular polyketide synthases (PKSs) catalyze dehydrations that occur frequently in the biosynthesis of complex polyketides, yet little is known about them structurally or mechanistically. Here, the structure of a DH domain, isolated from the fourth module of the erythromycin PKS, is presented at 1.85 A resolution. As with the DH of the highly related animalian fatty acid synthase, the DH monomer possesses a double-hotdog fold. Two symmetry mates within the crystal lattice make a contact that likely represents the DH dimerization interface within an intact PKS. Conserved hydrophobic residues on the DH surface indicate potential interfaces with two other PKS domains, the ketoreductase and the acyl carrier protein. Mutation of an invariant arginine at the hypothesized acyl carrier protein docking site in the context of the erythromycin PKS resulted in decreased production of the erythromycin precursor 6-deoxyerythronolide B. The structure elucidates how the alpha-hydrogen and beta-hydroxyl group of a polyketide substrate interact with the catalytic histidine and aspartic acid in the DH active site prior to dehydration.
PDB ID: 3EL6Download
MMDB ID: 67912
PDB Deposition Date: 2008/9/20
Updated in MMDB: 2008/12
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 3EL6: dimeric; determined by author and by software (PISA)
Molecular Components in 3EL6
Label Count Molecule
Proteins (2 molecules)
Erythromycin Dehydratase
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB