Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027
Abstract
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. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.
- Authors:
-
- The Scripps Research Institute, Jupiter, FL (United States); Shanghai Jiao Tong Univ., Shanghai (China)
- The Scripps Research Institute, Jupiter, FL (United States)
- The Scripps Research Institute, Jupiter, FL (United States); Purdue Univ., West Lafayette, IN (United States)
- Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Univ. of Wisconsin, Madison, WI (United States)
- Rice Univ., Houston, TX (United States); Jaypee Univ. of Information Technology, Himachal Pradesh (India)
- Rice Univ., Houston, TX (United States)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- Scripps Research Institute; German Research Foundation (DFG); National Institutes of Health (NIH), National Institute of General Medical Sciences; USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1374053
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- The Journal of Antibiotics
- Additional Journal Information:
- Journal Volume: 69; Journal Issue: 10; Journal ID: ISSN 0021-8820
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
Citation Formats
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, Jr., George N., and Shen, Ben. Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027. United States: N. p., 2016.
Web. doi:10.1038/ja.2016.88.
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, Jr., George N., & Shen, Ben. Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027. United States. https://doi.org/10.1038/ja.2016.88
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, Jr., George N., and Shen, Ben. Sat .
"Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027". United States. https://doi.org/10.1038/ja.2016.88. https://www.osti.gov/servlets/purl/1374053.
@article{osti_1374053,
title = {Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027},
author = {Huang, Tingting and Chang, Chin -Yuan and Lohman, Jeremy R. and Rudolf, Jeffrey D. and Kim, Youngchang and Chang, Changsoo and Yang, Dong and Ma, Ming and Yan, Xiaohui and Crnovcic, Ivana and Bigelow, Lance and Clancy, Shonda and Bingman, Craig A. and Yennamalli, Ragothaman M. and Babnigg, Gyorgy and Joachimiak, Andrzej and Phillips, Jr., George N. and Shen, Ben},
abstractNote = {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. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.},
doi = {10.1038/ja.2016.88},
journal = {The Journal of Antibiotics},
number = 10,
volume = 69,
place = {United States},
year = {Sat Oct 01 00:00:00 EDT 2016},
month = {Sat Oct 01 00:00:00 EDT 2016}
}
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Works referenced in this record:
CDD: NCBI's conserved domain database
journal, November 2014
- Marchler-Bauer, Aron; Derbyshire, Myra K.; Gonzales, Noreen R.
- Nucleic Acids Research, Vol. 43, Issue D1
Genes for Production of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus Are Clustered with the cagA Gene That Encodes the C-1027 Apoprotein
journal, February 2000
- Liu, Wen; Shen, Ben
- Antimicrobial Agents and Chemotherapy, Vol. 44, Issue 2
Crystal Structure of a Tetradecameric Assembly of the Association Domain of Ca2+/Calmodulin-Dependent Kinase II
journal, May 2003
- Hoelz, André; Nairn, Angus C.; Kuriyan, John
- Molecular Cell, Vol. 11, Issue 5
Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62.
journal, May 1995
- Paschal, B. M.; Gerace, L.
- Journal of Cell Biology, Vol. 129, Issue 4
The Calicheamicin Gene Cluster and Its Iterative Type I Enediyne PKS
journal, August 2002
- Ahlert, J.
- Science, Vol. 297, Issue 5584
Complexity and simplicity in the biosynthesis of enediyne natural products
journal, January 2010
- Liang, Zhao-Xun
- Natural Product Reports, Vol. 27, Issue 4
Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery
journal, August 2015
- Rudolf, Jeffrey D.; Yan, Xiaohui; Shen, Ben
- Journal of Industrial Microbiology & Biotechnology, Vol. 43, Issue 2-3
Structure of the polyketide cyclase SnoaL reveals a novel mechanism for enzymatic aldol condensation
journal, April 2004
- Sultana, Azmiri; Kallio, Pauli; Jansson, Anna
- The EMBO Journal, Vol. 23, Issue 9
The 1.6 Å Resolution Crystal Structure of Nuclear Transport Factor 2 (NTF2)
journal, July 1996
- Bullock, Timothy L.; Clarkson, David W.; Kent, Helen M.
- Journal of Molecular Biology, Vol. 260, Issue 3
The structure of neocarzinostatin chromophore possessing a novel bicyclo-[7,3,0]dodecadiyne system
journal, January 1985
- Edo, Kiyoto; Mizugaki, Michinao; Koide, Yoshio
- Tetrahedron Letters, Vol. 26, Issue 3
Dali server: conservation mapping in 3D
journal, May 2010
- Holm, Liisa; Rosenstr�m, P�ivi
- Nucleic Acids Research, Vol. 38, Issue suppl_2
Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model
journal, October 2003
- Liu, W.; Ahlert, J.; Gao, Q.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 21
Manipulation of pathway regulation in Streptomyces globisporus for overproduction of the enediyne antitumor antibiotic C-1027
journal, June 2010
- Chen, Yihua; Yin, Min; Horsman, Geoff P.
- The Journal of Antibiotics, Vol. 63, Issue 8
Characterization of the Maduropeptin Biosynthetic Gene Cluster from Actinomadura madurae ATCC 39144 Supporting a Unifying Paradigm for Enediyne Biosynthesis
journal, October 2007
- Van Lanen, Steven G.; Oh, Tae-jin; Liu, Wen
- Journal of the American Chemical Society, Vol. 129, Issue 43
Deciphering key features in protein structures with the new ENDscript server
journal, April 2014
- Robert, Xavier; Gouet, Patrice
- Nucleic Acids Research, Vol. 42, Issue W1
Unraveling the Biosynthesis of the Sporolide Cyclohexenone Building Block
journal, February 2008
- McGlinchey, Ryan P.; Nett, Markus; Moore, Bradley S.
- Journal of the American Chemical Society, Vol. 130, Issue 8
Biochemical Determination of Enzyme-Bound Metabolites: Preferential Accumulation of a Programmed Octaketide on the Enediyne Polyketide Synthase CalE8
journal, September 2013
- Belecki, Katherine; Townsend, Craig A.
- Journal of the American Chemical Society, Vol. 135, Issue 38
Ligation-independent cloning of PCR products (LIC-PCR)
journal, January 1990
- Aslanidis, Charalampos; de Jong, Pieter J.
- Nucleic Acids Research, Vol. 18, Issue 20
Leveraging structure for enzyme function prediction: methods, opportunities, and challenges
journal, August 2014
- Jacobson, Matthew P.; Kalyanaraman, Chakrapani; Zhao, Suwen
- Trends in Biochemical Sciences, Vol. 39, Issue 8
The Structural Biology Center 19ID undulator beamline: facility specifications and protein crystallographic results
journal, December 2005
- Rosenbaum, Gerd; Alkire, Randy W.; Evans, Gwyndaf
- Journal of Synchrotron Radiation, Vol. 13, Issue 1
Production of Octaketide Polyenes by the Calicheamicin Polyketide Synthase CalE8: Implications for the Biosynthesis of Enediyne Core Structures
journal, September 2009
- Belecki, Katherine; Crawford, Jason M.; Townsend, Craig A.
- Journal of the American Chemical Society, Vol. 131, Issue 35
Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes
journal, June 2010
- Horsman, G. P.; Chen, Y.; Thorson, J. S.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 25
Improvement of the Enediyne Antitumor Antibiotic C-1027 Production by Manipulating Its Biosynthetic Pathway Regulation in Streptomyces globisporus
journal, March 2011
- Chen, Yihua; Yin, Min; Horsman, Geoff P.
- Journal of Natural Products, Vol. 74, Issue 3
Rescue of deleterious mutations by the compensatory Y30F mutation in ketosteroid isomerase
journal, June 2013
- Cha, Hyung Jin; Jang, Do Soo; Kim, Yeon-Gil
- Molecules and Cells, Vol. 36, Issue 1
Filling out the structural map of the NTF2-like superfamily
journal, November 2013
- Eberhardt, Ruth Y.; Chang, Yuanyuan; Bateman, Alex
- BMC Bioinformatics, Vol. 14, Issue 1
Crystal structure and functional analysis of tetracenomycin ARO/CYC: Implications for cyclization specificity of aromatic polyketides
journal, April 2008
- Ames, B. D.; Korman, T. P.; Zhang, W.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 14
Environmental Control of the Calicheamicin Polyketide Synthase Leads to Detection of a Programmed Octaketide and a Proposal for Enediyne Biosynthesis
journal, October 2012
- Belecki, Katherine; Townsend, Craig A.
- Angewandte Chemie International Edition, Vol. 51, Issue 45
PROCHECK: a program to check the stereochemical quality of protein structures
journal, April 1993
- Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.
- Journal of Applied Crystallography, Vol. 26, Issue 2
The Neocarzinostatin Biosynthetic Gene Cluster from Streptomyces carzinostaticus ATCC 15944 Involving Two Iterative Type I Polyketide Synthases
journal, March 2005
- Liu, Wen; Nonaka, Koichi; Nie, Liping
- Chemistry & Biology, Vol. 12, Issue 3
The biosynthetic genes encoding for the production of the dynemicin enediyne core in Micromonospora chersina ATCC53710
journal, May 2008
- Gao, Qunjie; Thorson, Jon S.
- FEMS Microbiology Letters, Vol. 282, Issue 1
Biosynthesis of the Enediyne Antitumor Antibiotic C-1027
journal, August 2002
- Liu, W.
- Science, Vol. 297, Issue 5584
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
journal, May 2007
- Davis, I. W.; Leaver-Fay, A.; Chen, V. B.
- Nucleic Acids Research, Vol. 35, Issue Web Server
Designer enediynes generate DNA breaks, interstrand cross-links, or both, with concomitant changes in the regulation of DNA damage responses
journal, October 2007
- Kennedy, D. R.; Ju, J.; Shen, B.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 45
Single Chemical Modifications of the C-1027 Enediyne Core, a Radiomimetic Antitumor Drug, Affect Both Drug Potency and the Role of Ataxia-Telangiectasia Mutated in Cellular Responses to DNA Double-Strand Breaks
journal, January 2007
- Kennedy, D. R.; Gawron, L. S.; Ju, J.
- Cancer Research, Vol. 67, Issue 2
Mba1, a membrane-associated ribosome receptor in mitochondria
journal, April 2006
- Ott, Martin; Prestele, Martin; Bauerschmitt, Heike
- The EMBO Journal, Vol. 25, Issue 8
Crystal structure of scytalone dehydratase — a disease determinant of the rice pathogen, Magnaporthe grisea
journal, October 1994
- Lundqvist, Tomas; Rice, Janet; Hodge, C. Nicholas
- Structure, Vol. 2, Issue 10
Calculation of protein extinction coefficients from amino acid sequence data
journal, November 1989
- Gill, Stanley C.; von Hippel, Peter H.
- Analytical Biochemistry, Vol. 182, Issue 2
MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004
- Edgar, R. C.
- Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797
A genomics-guided approach for discovering and expressing cryptic metabolic pathways
journal, January 2003
- Zazopoulos, Emmanuel; Huang, Kexue; Staffa, Alfredo
- Nature Biotechnology, Vol. 21, Issue 2
C-1027, A Radiomimetic Enediyne Anticancer Drug, Preferentially Targets Hypoxic Cells
journal, January 2009
- Beerman, T. A.; Gawron, L. S.; Shin, S.
- Cancer Research, Vol. 69, Issue 2
PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin
journal, January 2003
- Gust, B.; Challis, G. L.; Fowler, K.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 4
Automation of protein purification for structural genomics
journal, March 2004
- Kim, Youngchang; Dementieva, Irina; Zhou, Min
- Journal of Structural and Functional Genomics, Vol. 5, Issue 1/2
Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics
journal, January 2013
- Lohman, Jeremy R.; Huang, Sheng-Xiong; Horsman, Geoffrey P.
- Molecular BioSystems, Vol. 9, Issue 3
A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis
journal, January 2008
- Zhang, J.; Van Lanen, S. G.; Ju, J.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 5, p. 1460-1465
Biosynthesis of Enediyne Antitumor Antibiotics
journal, April 2008
- Van Lanen, Steven; Shen, Ben
- Current Topics in Medicinal Chemistry, Vol. 8, Issue 6
Structures and Comparative Characterization of Biosynthetic Gene Clusters for Cyanosporasides, Enediyne-Derived Natural Products from Marine Actinomycetes
journal, March 2013
- Lane, Amy L.; Nam, Sang-Jip; Fukuda, Takashi
- Journal of the American Chemical Society, Vol. 135, Issue 11
SOLVE and RESOLVE: automated structure solution, density modification and model building
journal, November 2003
- Terwilliger, Thomas
- Journal of Synchrotron Radiation, Vol. 11, Issue 1
Environmental Control of the Calicheamicin Polyketide Synthase Leads to Detection of a Programmed Octaketide and a Proposal for Enediyne Biosynthesis
journal, October 2012
- Belecki, Katherine; Townsend, Craig A.
- Angewandte Chemie, Vol. 124, Issue 45
Cryo-EM structure of the respiratory syncytial virus RNA polymerase
journal, January 2020
- Cao, Dongdong; Gao, Yunrong; Roesler, Claire
- Nature Communications, Vol. 11, Issue 1
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
text, January 2007
- B., Chen, Vincent; C., Richardson, David; S., Richardson, Jane
- The University of North Carolina at Chapel Hill University Libraries
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journal, February 2020
- Lin, Chun-Yan; Pang, Ai-Ping; Zhang, Yue
- Microbial Cell Factories, Vol. 19, Issue 1