5JGL
Crystal structure of GtmA in complex with S-Adenosylmethionine
Summary for 5JGL
| Entry DOI | 10.2210/pdb5jgl/pdb |
| Descriptor | UbiE/COQ5 family methyltransferase, putative, S-ADENOSYLMETHIONINE, SODIUM ION, ... (4 entities in total) |
| Functional Keywords | aspergillus fumigatus, methyltransferase, s-adenosylmethionine, gliotoxin, resistance, transferase |
| Biological source | Aspergillus fumigatus |
| Total number of polymer chains | 2 |
| Total formula weight | 65754.68 |
| Authors | Dolan, S.K.,Bock, T.,Hering, V.,Jones, G.W.,Blankenfeldt, W.,Doyle, S. (deposition date: 2016-04-20, release date: 2017-03-01, Last modification date: 2024-05-08) |
| Primary citation | Dolan, S.K.,Bock, T.,Hering, V.,Owens, R.A.,Jones, G.W.,Blankenfeldt, W.,Doyle, S. Structural, mechanistic and functional insight into gliotoxinbis-thiomethylation inAspergillus fumigatus. Open Biol, 7:-, 2017 Cited by PubMed Abstract: Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin -methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to -adenosylhomocysteine (1.33 Å) and GtmA complexed to -adenosylmethionine (2.28 Å), providing mechanistic insights into this important biotransformation. We further reveal that simultaneous elimination of the ability of to dissipate highly reactive dithiol gliotoxin, via deletion of GliT and GtmA, results in the most significant hypersensitivity to exogenous gliotoxin observed to date. Indeed, quantitative proteomic analysis of Δ::Δ reveals an uncontrolled over-activation of the -cluster upon gliotoxin exposure. The data presented herein reveal, for the first time, the extreme risk associated with intracellular dithiol gliotoxin biosynthesis-in the absence of an efficient dismutation capacity. Significantly, a previously concealed protective role for GtmA and functionality of ETP -thiomethylation as an ancestral protection strategy against dithiol compounds is now evident. PubMed: 28179499DOI: 10.1098/rsob.160292 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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