6bk3 | pdb_00006bk3
Crystal structure of Os79 from O. sativa in complex with UDP and deoxynivalenol-3-glucoside (glucose moitey not resolved)
Structural highlights
Function[UGT79_ORYSJ] Involved in the detoxification of the Fusarium mycotoxin deoxynivalenol by the transfer of glucose from UDP-D-glucose to the hydroxyl group at C-3, forming deoxynivalenol-3-O-beta-D-glucoside.[1] [2] Publication Abstract from PubMedFamily 1 UDP-glycosyltransferases in plants (UGTs) primarily form glucose conjugates of small molecules and, besides other functions, play a role in detoxification of xenobiotics. Indeed, overexpression of a barley UGT in wheat has been shown to control Fusarium head blight, where this is a plant disease of global significance that leads to reduced crop yields and contamination with trichothecene mycotoxins such as deoxynivalenol (DON), T-2 toxin and many other structural variants. The UGT Os79 from rice has emerged as a promising candidate for inactivation of mycotoxins on account of its ability to glycosylate DON, nivalenol and hydrolyzed T-2 toxin (HT-2). However, Os79 is unable to modify T-2 toxin (T-2), produced by pathogens such as F. sporotrichioides and F. langsethii. Activity towards T-2 is desirable because it would allow a single UGT to inactivate co-occurring mycotoxins. Here, the structure of Os79 in complex with the products, UDP and deoxynivalenol-3-O-glucoside is reported together with a kinetic analysis of a broad range of trichothecene mycotoxins. Residues associated with the trichothecene binding pocket were examined by site-directed mutagenesis which revealed that trichothecenes substituted on the C4 position, which are not glycosylated by WT Os79, can be accommodated in the binding pocket by increasing its volume. The triple mutation H122A/L123A/Q202L, which increases the volume of the active site and attenuates polar contacts, led to strong and equivalent activity towards trichothecenes with C4 acetyl groups. This mutant enzyme provides the broad specificity required to control multiple toxins produced by different Fusarium species and chemotypes. Determinants and Expansion of Specificity in a Trichothecene UDP-glucosyltransferase from Oryza sativa.,Wetterhorn KM, Gabardi K, Michlmayr H, Malachova A, Busman M, McCormick SP, Berthiller F, Adam G, Rayment I Biochemistry. 2017 Nov 15. doi: 10.1021/acs.biochem.7b01007. PMID:29140092[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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