4YUC

Crystal Structure of CorB derivatized with S-(2-acetamidoethyl) 4-methyl-3-oxohexanethioate

Summary for 4YUC

• Entry DOI: 10.2210/pdb4yuc/pdb
• Descriptor: CorB, (4S)-2-METHYL-2,4-PENTANEDIOL, SODIUM ION, ... (4 entities in total)
• Functional Keywords: interconnecting ketosynthase, thiolase superfamily, s-(2-acetamidoethyl) 4-methyl-3-oxohexanethioate, hydrolase
• Biological source: Corallococcus coralloides
• Total number of polymer chains: 1
• Total formula weight: 36786.07

Authors

Zocher, G.,Vilstrup, J.,Stehle, T. (deposition date: 2015-03-18, release date: 2016-03-30, Last modification date: 2024-05-08)

Primary citation

Zocher, G.,Vilstrup, J.,Heine, D.,Hallab, A.,Goralski, E.,Hertweck, C.,Stahl, M.,Schaberle, T.F.,Stehle, T.
Structural basis of head to head polyketide fusion by CorB.
Chem Sci, 6:6525-6536, 2015

PubMed Abstract: Corallopyronin A is a polyketide derived from the myxobacterium with potent antibiotic features. The gene cluster responsible for the biosynthesis of corallopyronin A has been described recently, and it was proposed that CorB acts as a ketosynthase to interconnect two polyketide chains in a rare head-to-head condensation reaction. We determined the structure of CorB, the interconnecting polyketide synthase, to high resolution and found that CorB displays a thiolase fold. Site-directed mutagenesis showed that the catalytic triad consisting of a cysteine, a histidine and an asparagine is crucial for catalysis, and that this triad shares similarities with the triad found in HMG-CoA synthases. We synthesized a substrate mimic to derivatize purified CorB and confirmed substrate attachment by ESI-MS. Structural analysis of the complex yielded an electron density-based model for the polyketide chain and showed that the unusually wide, T-shaped active site is able to accommodate two polyketides simultaneously. Our structural analysis provides a platform for understanding the unusual head-to-head polyketide-interconnecting reaction catalyzed by CorB.

PubMed: 28757960
DOI: 10.1039/c5sc02488a

Experimental method

X-RAY DIFFRACTION (1.31 Å)