Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis

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dc.citation.firstpage5159en_US
dc.citation.issueNumber8en_US
dc.citation.journalTitleACS Omegaen_US
dc.citation.lastpage5169en_US
dc.citation.volumeNumber2en_US
dc.contributor.authorAnnaval, Thibaulten_US
dc.contributor.authorRudolf, Jeffrey D.en_US
dc.contributor.authorChang, Chin-Yuanen_US
dc.contributor.authorLohman, Jeremy R.en_US
dc.contributor.authorKim, Youngchangen_US
dc.contributor.authorBigelow, Lanceen_US
dc.contributor.authorJedrzejczak, Roberten_US
dc.contributor.authorBabnigg, Gyorgyen_US
dc.contributor.authorJoachimiak, Andrzejen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.contributor.authorShen, Benen_US
dc.date.accessioned2017-10-06T18:43:16Zen_US
dc.date.available2017-10-06T18:43:16Zen_US
dc.date.issued2017en_US
dc.description.abstractEnediynes are potent natural product anticancer antibiotics, and are classified as 9- or 10-membered according to the size of their enediyne core carbon skeleton. Both 9- and 10-membered enediyne cores are biosynthesized by the enediyne polyketide synthase (PKSE), thioesterase (TE), and PKSE-associated enzymes. Although the divergence between 9- and 10-membered enediyne core biosynthesis remains unclear, it has been observed that nascent polyketide intermediates, tethered to the acyl carrier protein (ACP) domain of PKSE, could be released by TE in the absence of the PKSE-associated enzymes. In this study, we determined the crystal structure of SgcE10, the TE that participates in the biosynthesis of the 9-membered enediyne C-1027. Structural comparison of SgcE10 with CalE7 and DynE7, two TEs that participate in the biosynthesis of the 10-membered enediynes calicheamicin and dynemicin, respectively, revealed that they share a common α/β hot-dog fold. The amino acids involved in both substrate binding and catalysis are conserved among SgcE10, CalE7, and DynE7. The volume and the shape of the substrate-binding channel and active site in SgcE10, CalE7, and DynE7 confirm that TEs from both 9- and 10-membered enediyne biosynthetic machineries bind the linear form of similar ACP-tethered polyene intermediates. Taken together, these findings further support the proposal that the divergence between 9- and 10-membered enediyne core biosynthesis occurs beyond PKSE and TE catalysis.en_US
dc.identifier.citationAnnaval, Thibault, Rudolf, Jeffrey D., Chang, Chin-Yuan, et al.. "Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis." <i>ACS Omega,</i> 2, no. 8 (2017) American Chemical Society: 5159-5169. https://doi.org/10.1021/acsomega.7b00933.en_US
dc.identifier.digitalCrystal_Structure_Thioesterase_SgcE10en_US
dc.identifier.doihttps://doi.org/10.1021/acsomega.7b00933en_US
dc.identifier.urihttps://hdl.handle.net/1911/97774en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.en_US
dc.rights.urihttp://pubs.acs.org/page/policy/authorchoice_termsofuse.htmlen_US
dc.titleCrystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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