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dc.contributor.authorAnnaval, Thibault
Rudolf, Jeffrey D.
Chang, Chin-Yuan
Lohman, Jeremy R.
Kim, Youngchang
Bigelow, Lance
Jedrzejczak, Robert
Babnigg, Gyorgy
Joachimiak, Andrzej
Phillips, George N. Jr.
Shen, Ben
dc.date.accessioned 2017-10-06T18:43:16Z
dc.date.available 2017-10-06T18:43:16Z
dc.date.issued 2017
dc.identifier.citation Annaval, 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." ACS Omega, 2, no. 8 (2017) American Chemical Society: 5159-5169. https://doi.org/10.1021/acsomega.7b00933.
dc.identifier.urihttps://hdl.handle.net/1911/97774
dc.description.abstract Enediynes 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.
dc.language.iso eng
dc.publisher American Chemical Society
dc.rights This 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.
dc.rights.urihttp://pubs.acs.org/page/policy/authorchoice_termsofuse.html
dc.title Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis
dc.type Journal article
dc.citation.journalTitle ACS Omega
dc.citation.volumeNumber 2
dc.citation.issueNumber 8
dc.identifier.digital Crystal_Structure_Thioesterase_SgcE10
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1021/acsomega.7b00933
dc.identifier.pmcid PMC5579567
dc.identifier.pmid 28884166
dc.type.publication publisher version
dc.citation.firstpage 5159
dc.citation.lastpage 5169


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