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Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis
Zhang, CS; Bitto, E; Goff, RD; Singh, S; Bingman, CA; Griffith, BR; Albermann, C; Phillips, GN; Thorson, JS; phillips@biochem.wisc.edu; jsthorson@pharmacy.wisc.edu
2008
发表期刊CHEMISTRY & BIOLOGY
ISSN1074-5521
卷号15期号:8页码:842-853
摘要The enediyne antibiotic calicheamicin (CLM) gamma(I)(1) is a prominent antitumor agent that is targeted to DNA by a novel aryltetrasaccharide comprised of an aromatic unit and four unusual carbohydrates. Herein we report the heterologous expression and the biochemical characterization of the two "internal" glycosyltransferases CaIG3 and CaIG2 and the structural elucidation of an enediyne glycosyltransferase (CaIG3). In conjunction with the previous characterization of the "external" CLM GTs CaIG1 and CaIG4, this study completes the functional assignment of all four CLM GTs, extends the utility of enediyne GT-catalyzed reaction reversibility, and presents conclusive evidence of a sequential glycosylation pathway in CLM biosynthesis. This work also reveals the common GT-B structural fold can now be extended to include enediyne GTs.
部门归属[Bitto, Eduard; Bingman, Craig A.; Phillips, George N., Jr.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA; [Zhang, Changsheng] Chinese Acad Sci, S China Sea Inst Oceanol, Guangdong Key Lab Marine Mat Med, Guangzhou 510301, Peoples R China; [Goff, Randal D.; Singh, Shanteri; Griffith, Byron R.; Albermann, Christoph; Thorson, Jon S.] Univ Wisconsin, Lab Biosynthet Chem, Div Pharmaceut Sci, Sch Pharm,Natl Cooperat Drug Discovery Grp Progra, Madison, WI 53706 USA
学科领域Biochemistry & Molecular Biology
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收录类别sci
资助项目广东省海洋药物重点实验室
WOS记录号WOS:000258940000012
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文献类型期刊论文
条目标识符http://ir.scsio.ac.cn/handle/344004/5266
专题广东省海洋药物重点实验室
通讯作者phillips@biochem.wisc.edu; jsthorson@pharmacy.wisc.edu
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Zhang, CS,Bitto, E,Goff, RD,et al. Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis[J]. CHEMISTRY & BIOLOGY,2008,15(8):842-853.
APA Zhang, CS.,Bitto, E.,Goff, RD.,Singh, S.,Bingman, CA.,...&jsthorson@pharmacy.wisc.edu.(2008).Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis.CHEMISTRY & BIOLOGY,15(8),842-853.
MLA Zhang, CS,et al."Biochemical and structural insights of the early glycosylation steps in calicheamicin biosynthesis".CHEMISTRY & BIOLOGY 15.8(2008):842-853.
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