4yuc
Crystal Structure of CorB derivatized with S-(2-acetamidoethyl) 4-methyl-3-oxohexanethioateCrystal Structure of CorB derivatized with S-(2-acetamidoethyl) 4-methyl-3-oxohexanethioate
Structural highlights
FunctionPublication Abstract from PubMedCorallopyronin A is a polyketide derived from the myxobacterium Corallococcus coralloides 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. Structural basis of head to head polyketide fusion by CorB.,Zocher G, Vilstrup J, Heine D, Hallab A, Goralski E, Hertweck C, Stahl M, Schaberle TF, Stehle T Chem Sci. 2015 Nov 13;6(11):6525-6536. doi: 10.1039/c5sc02488a. Epub 2015 Aug 6. PMID:28757960[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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