7YP3

Crystal structure of elaiophylin glycosyltransferase in complex with elaiophylin

Summary for 7YP3

• Entry DOI: 10.2210/pdb7yp3/pdb
• Descriptor: Glycosyltransferase, ACETATE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: glycosyltransferase, elaiophylin, gt1, transferase
• Biological source: Streptomyces sp. SCSIO 01934
• Total number of polymer chains: 7
• Total formula weight: 346780.71

Authors

Xu, T.,Liu, Q.,Gan, Q.,Liu, J. (deposition date: 2022-08-02, release date: 2022-11-02, Last modification date: 2023-11-29)

Primary citation

Xu, T.,Gan, Q.,Liu, Q.,Chen, R.,Zhen, X.,Zhang, C.,Liu, J.
Substrate-induced dimerization of elaiophylin glycosyltransferase reveals a novel self-activating form of glycosyltransferase for symmetric glycosylation.
Acta Crystallogr D Struct Biol, 78:1235-1248, 2022

PubMed Abstract: Elaiophylin (Ela), a unique 16-membered symmetric macrodiolide antibiotic, displays broad biological activity. Two rare 2-deoxy-L-fucose moieties at the ends of Ela are critical for its activity. Previously, elaiophylin glycosyltransferase (ElaGT) was identified as the enzyme that is responsible for the symmetric glycosylation of Ela, acting as a potential enzymatic tool for enhancing the diversity and activity of Ela. However, a symmetric catalytic mechanism has never been reported for a glycosyltransferase (GT). To explore the catalytic mechanism, the structure of ElaGT was determined in four forms: the apo form and Ela-bound, thymidine diphosphate-bound and uridine diphosphate-bound forms. In the Ela-bound structure, two ElaGTs form a `face-to-face' C2-symmetric homodimer with a continuous acceptor-binding pocket, allowing a molecule of Ela to shuffle through. Interestingly, this dimer interface resembles that of the activator-dependent GT EryCIII with its activator EryCII. Sequence analysis also indicates that ElaGT belongs to the activator-dependent GT family, but no putative activator has been identified in the Ela gene cluster. It was then found that the ElaGT homodimer may utilize this `face-to-face' arrangement to stabilize the Ela-binding loops on the interface and to simultaneously allosterically regulate the catalytic center. Therefore, these structures present a novel self-activating model for symmetric sugar transfer in the GT family and a new potential regulation site for substrate specificity.

PubMed: 36189743
DOI: 10.1107/S2059798322008658

Experimental method

X-RAY DIFFRACTION (2.1 Å)