Über das Acceptorsubstrat der C‐Glycosyltransferase UrdGT2: drei Prejadomycin‐C‐glycoside aus einer konstruierten Mutante von Streptomyces globisporus 1912 ΔlndE(urdGT2)

Strukturen der O-Glycosyltransferase LanGT2 und der generierten C-Glycosyltransferase LanGT2S8Ac zeigen, dass der Austausch eines kurzen Peptidfragments die Funktionalität eines Enzyms deutlich verändern kann. Eine synthetische TDP-Carbaolivose wurde mit den Enzymen kokristallisiert. Es zeigte sich, dass die Bindung des Carbazuckers zu einer Konformationsänderung des Enzyms führt, die dann eine Bindestelle für ein Aglykonsubstrat erzeugt. Obwohl eine Bindung des Aglykons nicht experimentell nachgewiesen wurde, deuten Docking-Studien auf unterschiedliche Bindungsmodi im Fall von O-bzw. C-Glycosylierung hin.

show abstract

Strukturelle Charakterisierung von O‐ und C‐glycosylierenden Varianten der Landomycin‐Glycosyltransferase LanGT2

Tam

Härle

Gerhardt

et al. 2015

Angewandte Chemie

Self Cite

View full text Add to dashboard Cite

show abstract

Structural Characterization of O‐ and C‐Glycosylating Variants of the Landomycin Glycosyltransferase LanGT2

et al. 2015

Self Cite

View full text Add to dashboard Cite

The structures of the O-glycosyltransferase LanGT2 and the engineered, C—C bond-forming variant LanGT2S8Ac show how the replacement of a single loop can change the functionality of the enzyme. Crystal structures of the enzymes in complex with a nonhydrolyzable nucleotide-sugar analogue revealed that there is a conformational transition to create the binding sites for the aglycon substrate. This induced-fit transition was explored by molecular docking experiments with various aglycon substrates.

show abstract

Generation of New Landomycins with Altered Saccharide Patterns through Over‐expression of the Glycosyltransferase Gene lanGT3 in the Biosynthetic Gene Cluster of Landomycin A in Streptomyces cyanogenus S‐136

et al. 2006

Self Cite

View full text Add to dashboard Cite

Two novel landomycin compounds, landomycins I and J, were generated with a new mutant strain of Streptomyces cyanogenus in which the glycosyltransferase that is encoded by lanGT3 was overexpressed. This mutant also produced the known landomycins A, B, and D. All these compounds consist ofthe same polyketide-derived aglycon but differ in their sugar moieties, which are chains of different lengths. The major new metabolite, landomycin J, was found to consist of landomycinone with a tetrasaccharide chain attached. Combined with previous results ofthe production oflandomycin E (which contains three sugars) by the LanGT3 -mutant strain (obtained by targeted gene deletion of lanGT3), it was verified that LanGT3 is a D-olivosyltransferase responsible for the transfer of the fourth sugar required for landomycin A biosynthesis. The experiments also showed that gene overexpression is a powerful method for unbalancing biosynthetic pathways in order to generate new metabolites. The cytotoxicity ofthe new landomycins-compared to known ones-was assessed by using three different tumor cell lines, and their structure-activity relationship (SAR) with respect to the length ofthe deoxysugar side chain was deduced from the results.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Über das Acceptorsubstrat der C‐Glycosyltransferase UrdGT2: drei Prejadomycin‐C‐glycoside aus einer konstruierten Mutante von Streptomyces globisporus 1912 ΔlndE(urdGT2)

Cited by 9 publications

References 28 publications

Strukturelle Charakterisierung von O‐ und C‐glycosylierenden Varianten der Landomycin‐Glycosyltransferase LanGT2

Strukturelle Charakterisierung von O‐ und C‐glycosylierenden Varianten der Landomycin‐Glycosyltransferase LanGT2

Structural Characterization of O‐ and C‐Glycosylating Variants of the Landomycin Glycosyltransferase LanGT2

Generation of New Landomycins with Altered Saccharide Patterns through Over‐expression of the Glycosyltransferase Gene lanGT3 in the Biosynthetic Gene Cluster of Landomycin A in Streptomyces cyanogenus S‐136

Contact Info

Product

Resources

About