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dc.contributor.authorElshahawi, Sherif I.
Ramelot, Theresa A.
Seetharaman, Jayaraman
Chen, Jing
Singh, Shanteri
Yang, Yunhuang
Pederson, Kari
Kharel, Madan K.
Xiao, Rong
Lew, Scott
Yennamalli, Ragothaman M.
Miller, Mitchell D.
Wang, Fengbin
Tong, Liang
Montelione, Gaetano T.
Kennedy, Michael A.
Bingman, Craig A.
Zhu, Haining
Phillips, George N. Jr.
Thorson, Jon S.
dc.date.accessioned 2016-01-29T22:36:34Z
dc.date.available 2016-01-29T22:36:34Z
dc.date.issued 2014
dc.identifier.citation Elshahawi, Sherif I., Ramelot, Theresa A., Seetharaman, Jayaraman, et al.. "Structure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19." ACS Chemical Biology, 9, no. 10 (2014) American Chemical Society: 2347-2358. http://dx.doi.org/10.1021/cb500327m.
dc.identifier.urihttps://hdl.handle.net/1911/88287
dc.description.abstract Calicheamicin γ1I (1) is an enediyne antitumor compound produced by Micromonospora echinospora spp. calichensis, and its biosynthetic gene cluster has been previously reported. Despite extensive analysis and biochemical study, several genes in the biosynthetic gene cluster of 1 remain functionally unassigned. Using a structural genomics approach and biochemical characterization, two proteins encoded by genes from the 1 biosynthetic gene cluster assigned as “unknowns”, CalU16 and CalU19, were characterized. Structure analysis revealed that they possess the STeroidogenic Acute Regulatory protein related lipid Transfer (START) domain known mainly to bind and transport lipids and previously identified as the structural signature of the enediyne self-resistance protein CalC. Subsequent study revealed calU16 and calU19 to confer resistance to 1, and reminiscent of the prototype CalC, both CalU16 and CalU19 were cleaved by 1 in vitro. Through site-directed mutagenesis and mass spectrometry, we identified the site of cleavage in each protein and characterized their function in conferring resistance against 1. This report emphasizes the importance of structural genomics as a powerful tool for the functional annotation of unknown proteins.
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 Structure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19
dc.type Journal article
dc.citation.journalTitle ACS Chemical Biology
dc.citation.volumeNumber 9
dc.citation.issueNumber 10
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1021/cb500327m
dc.identifier.pmcid PMC4201346
dc.identifier.pmid 25079510
dc.type.publication publisher version
dc.citation.firstpage 2347
dc.citation.lastpage 2358


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