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Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027

Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies,...

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Autores principales: Huang, Tingting, Chang, Chin-Yuan, Lohman, Jeremy R., Rudolf, Jeffrey D., Kim, Youngchang, Chang, Changsoo, Yang, Dong, Ma, Ming, Yan, Xiaohui, Crnovcic, Ivana, Bigelow, Lance, Clancy, Shonda, Bingman, Craig A., Yennamalli, Ragothaman M., Babnigg, Gyorgy, Joachimiak, Andrzej, Phillips, George N., Shen, Ben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083130/
https://www.ncbi.nlm.nih.gov/pubmed/27406907
http://dx.doi.org/10.1038/ja.2016.88
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author Huang, Tingting
Chang, Chin-Yuan
Lohman, Jeremy R.
Rudolf, Jeffrey D.
Kim, Youngchang
Chang, Changsoo
Yang, Dong
Ma, Ming
Yan, Xiaohui
Crnovcic, Ivana
Bigelow, Lance
Clancy, Shonda
Bingman, Craig A.
Yennamalli, Ragothaman M.
Babnigg, Gyorgy
Joachimiak, Andrzej
Phillips, George N.
Shen, Ben
author_facet Huang, Tingting
Chang, Chin-Yuan
Lohman, Jeremy R.
Rudolf, Jeffrey D.
Kim, Youngchang
Chang, Changsoo
Yang, Dong
Ma, Ming
Yan, Xiaohui
Crnovcic, Ivana
Bigelow, Lance
Clancy, Shonda
Bingman, Craig A.
Yennamalli, Ragothaman M.
Babnigg, Gyorgy
Joachimiak, Andrzej
Phillips, George N.
Shen, Ben
author_sort Huang, Tingting
collection PubMed
description Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us to propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase associated enzymes, into an enzyme-sequestered enediyne core intermediate. These findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in 9-membered enediyne core biosynthesis.
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spelling pubmed-50831302017-01-13 Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027 Huang, Tingting Chang, Chin-Yuan Lohman, Jeremy R. Rudolf, Jeffrey D. Kim, Youngchang Chang, Changsoo Yang, Dong Ma, Ming Yan, Xiaohui Crnovcic, Ivana Bigelow, Lance Clancy, Shonda Bingman, Craig A. Yennamalli, Ragothaman M. Babnigg, Gyorgy Joachimiak, Andrzej Phillips, George N. Shen, Ben J Antibiot (Tokyo) Article Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us to propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase associated enzymes, into an enzyme-sequestered enediyne core intermediate. These findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in 9-membered enediyne core biosynthesis. 2016-07-13 2016-10 /pmc/articles/PMC5083130/ /pubmed/27406907 http://dx.doi.org/10.1038/ja.2016.88 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Huang, Tingting
Chang, Chin-Yuan
Lohman, Jeremy R.
Rudolf, Jeffrey D.
Kim, Youngchang
Chang, Changsoo
Yang, Dong
Ma, Ming
Yan, Xiaohui
Crnovcic, Ivana
Bigelow, Lance
Clancy, Shonda
Bingman, Craig A.
Yennamalli, Ragothaman M.
Babnigg, Gyorgy
Joachimiak, Andrzej
Phillips, George N.
Shen, Ben
Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027
title Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027
title_full Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027
title_fullStr Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027
title_full_unstemmed Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027
title_short Crystal Structure of SgcJ, An NTF2-Like Superfamily Protein Involved in Biosynthesis of the 9-Membered Enediyne Antitumor Antibiotic C-1027
title_sort crystal structure of sgcj, an ntf2-like superfamily protein involved in biosynthesis of the 9-membered enediyne antitumor antibiotic c-1027
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083130/
https://www.ncbi.nlm.nih.gov/pubmed/27406907
http://dx.doi.org/10.1038/ja.2016.88
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