4I4J

The structure of SgcE10, the ACP-polyene thioesterase involved in C-1027 biosynthesis

Summary for 4I4J

• Entry DOI: 10.2210/pdb4i4j/pdb
• Descriptor: ACP-polyene thioesterase, D(-)-TARTARIC ACID, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: structural genomics, psi-biology, midwest center for structural genomics, mcsg, enzyme discovery for natural product biosynthesis, natpro, alpha-beta fold, hot-dog fold, esterase, hydrolase
• Biological source: Streptomyces globisporus
• Total number of polymer chains: 8
• Total formula weight: 145856.66

Authors

Kim, Y.,Bigelow, L.,Bearden, J.,Babnigg, J.,Bingman, C.A.,Yennamalli, R.,Lohman, J.,Ma, M.,Shen, B.,Phillips Jr., G.N.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Enzyme Discovery for Natural Product Biosynthesis (NatPro) (deposition date: 2012-11-27, release date: 2012-12-12, Last modification date: 2024-11-06)

Primary citation

Annaval, T.,Rudolf, J.D.,Chang, C.Y.,Lohman, J.R.,Kim, Y.,Bigelow, L.,Jedrzejczak, R.,Babnigg, G.,Joachimiak, A.,Phillips Jr., G.N.,Shen, B.
Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis.
Acs Omega, 2:5159-5169, 2017

PubMed 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.

PubMed: 28884166
DOI: 10.1021/acsomega.7b00933

Experimental method

X-RAY DIFFRACTION (2.784 Å)