Structure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19

Simple item page
dc.citation.firstpage2347en_US
dc.citation.issueNumber10en_US
dc.citation.journalTitleACS Chemical Biologyen_US
dc.citation.lastpage2358en_US
dc.citation.volumeNumber9en_US
dc.contributor.authorElshahawi, Sherif I.en_US
dc.contributor.authorRamelot, Theresa A.en_US
dc.contributor.authorSeetharaman, Jayaramanen_US
dc.contributor.authorChen, Jing Hanen_US
dc.contributor.authorSingh, Shanterien_US
dc.contributor.authorYang, Yunhuangen_US
dc.contributor.authorPederson, Karien_US
dc.contributor.authorKharel, Madan K.en_US
dc.contributor.authorXiao, Rongen_US
dc.contributor.authorLew, Scotten_US
dc.contributor.authorYennamalli, Ragothaman M.en_US
dc.contributor.authorMiller, Mitchell D.en_US
dc.contributor.authorWang, Fengbinen_US
dc.contributor.authorTong, Liangen_US
dc.contributor.authorMontelione, Gaetano T.en_US
dc.contributor.authorKennedy, Michael A.en_US
dc.contributor.authorBingman, Craig A.en_US
dc.contributor.authorZhu, Hainingen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.contributor.authorThorson, Jon S.en_US
dc.date.accessioned2016-01-29T22:36:34Zen_US
dc.date.available2016-01-29T22:36:34Zen_US
dc.date.issued2014en_US
dc.description.abstractCalicheamicin 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.en_US
dc.identifier.citationElshahawi, Sherif I., Ramelot, Theresa A., Seetharaman, Jayaraman, et al.. "Structure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19." <i>ACS Chemical Biology,</i> 9, no. 10 (2014) American Chemical Society: 2347-2358. http://dx.doi.org/10.1021/cb500327m.en_US
dc.identifier.doihttp://dx.doi.org/10.1021/cb500327men_US
dc.identifier.urihttps://hdl.handle.net/1911/88287en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis 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.en_US
dc.rights.urihttp://pubs.acs.org/page/policy/authorchoice_termsofuse.htmlen_US
dc.titleStructure-Guided Functional Characterization of Enediyne Self-Sacrifice Resistance Proteins, CalU16 and CalU19en_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
cb500327m.pdf
Size:
6.15 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Faculty Publications
Biochemistry and Cell Biology Publications