Enzymes
UniProtKB help_outline | 1 proteins |
Enzyme class help_outline |
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Reaction participants Show >> << Hide
- Name help_outline aklavinone Identifier CHEBI:31181 (Beilstein: 3041138; CAS: 16234-96-1) help_outline Charge 0 Formula C22H20O8 InChIKeyhelp_outline RACGRCLGVYXIAO-YOKWENHESA-N SMILEShelp_outline CC[C@@]1(O)C[C@H](O)c2c(O)c3C(=O)c4c(O)cccc4C(=O)c3cc2[C@H]1C(=O)OC 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline dTDP-β-L-rhodosamine Identifier CHEBI:78301 Charge -1 Formula C18H30N3O13P2 InChIKeyhelp_outline XPIWJCQKSXFPJI-WYVHVMBXSA-M SMILEShelp_outline C[C@@H]1O[C@@H](C[C@@H]([C@@H]1O)[NH+](C)C)OP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H](C[C@@H]1O)n1cc(C)c(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline aclacinomycin T Identifier CHEBI:77979 Charge 0 Formula C30H35NO10 InChIKeyhelp_outline LJZPVWKMAYDYAS-QKKPTTNWSA-N SMILEShelp_outline CC[C@@]1(O)C[C@H](O[C@H]2C[C@@H]([C@H](O)[C@H](C)O2)[NH+](C)C)c2c([O-])c3C(=O)c4c(O)cccc4C(=O)c3cc2[C@H]1C(=O)OC 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline dTDP Identifier CHEBI:58369 Charge -3 Formula C10H13N2O11P2 InChIKeyhelp_outline UJLXYODCHAELLY-XLPZGREQSA-K SMILEShelp_outline Cc1cn([C@H]2C[C@H](O)[C@@H](COP([O-])(=O)OP([O-])([O-])=O)O2)c(=O)[nH]c1=O 2D coordinates Mol file for the small molecule Search links Involved in 31 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:41564 | RHEA:41565 | RHEA:41566 | RHEA:41567 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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AknT is an activating protein for the glycosyltransferase AknS in L-aminodeoxysugar transfer to the aglycone of aclacinomycin A.
Lu W., Leimkuhler C., Gatto G.J. Jr., Kruger R.G., Oberthuer M., Kahne D., Walsh C.T.
During biosynthesis of the anthracycline antitumor agents daunomycin, adriamycin, and aclacinomycin, the polyketide-derived tetracyclic aglycone is enzymatically glycosylated at the C7-OH by dedicated glycosyltransferases (Gtfs) that transfer L-2,3,6-trideoxy-3-aminohexoses. In aclacinomycins, the ... >> More
During biosynthesis of the anthracycline antitumor agents daunomycin, adriamycin, and aclacinomycin, the polyketide-derived tetracyclic aglycone is enzymatically glycosylated at the C7-OH by dedicated glycosyltransferases (Gtfs) that transfer L-2,3,6-trideoxy-3-aminohexoses. In aclacinomycins, the first deoxyhexose is predicted to be transferred via AknS action, then subjected to further elongation to a trisaccharide by the subsequent Gtf, AknK. We report here that purified AknS has very low activity in the absence of the adjacently encoded AknT; however, at a 3:1 ratio, AknT stimulates AknS k(cat) by 40-fold up to 0.22 min(-1) for transfer of L-2-deoxyfucose (2-dF) to the aglycone aklavinone. It is likely that several other Gtfs that glycosylate polyketide aglycones also act as two-component catalytic systems. Incubations of purified AknS/AknT/AknK with two aglycones and two dTDP-2-deoxyhexoses produced previously uncharacterized anthracycline disaccharides. << Less
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Characterization of rhodosaminyl transfer by the AknS/AknT glycosylation complex and its use in reconstituting the biosynthetic pathway of aclacinomycin A.
Leimkuhler C., Fridman M., Lupoli T., Walker S., Walsh C.T., Kahne D.
The tetracyclic core of anthracycline natural products with antitumor activity such as aclacinomycin A are tailored during biosynthesis by regioselective glycosylation. We report the first synthesis of TDP-L-rhodosamine and demonstrate that the glycosyltransferase AknS transfers L-rhodosamine to t ... >> More
The tetracyclic core of anthracycline natural products with antitumor activity such as aclacinomycin A are tailored during biosynthesis by regioselective glycosylation. We report the first synthesis of TDP-L-rhodosamine and demonstrate that the glycosyltransferase AknS transfers L-rhodosamine to the aglycone to initiate construction of the side-chain trisaccharide. The partner protein AknT accelerates AknS turnover rate for L-rhodosamine transfer by 200-fold. AknT does not affect the Km but rather affects the kcat. Using these data, we propose that AknT causes a conformational change in AknS that stabilizes the transition state and ultimately enhances transfer. When the subsequent glycosyltransferase AknK and its substrate TDP-L-fucose are also added to the aglycone, the disaccharide and low levels of a fully reconstituted trisaccharide form of aclacinomycin are observed. << Less
J. Am. Chem. Soc. 129:10546-10550(2007) [PubMed] [EuropePMC]