5jgj | pdb_00005jgj

Crystal structure of GtmA

spinqualitylabelsall models 5jgj, resolution 1.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jgj is a 1 chain structure with sequence from Aspergillus fumigatus z5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: Y699_02735 (Aspergillus fumigatus Z5) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 Aspergillus fumigatus Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin S-methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 A), GtmA complexed to S-adenosylhomocysteine (1.33 A) and GtmA complexed to S-adenosylmethionine (2.28 A), providing mechanistic insights into this important biotransformation. We further reveal that simultaneous elimination of the ability of A. fumigatus 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 DeltagliT::DeltagtmA reveals an uncontrolled over-activation of the gli-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 bis-thiomethylation as an ancestral protection strategy against dithiol compounds is now evident. Structural, mechanistic and functional insight into gliotoxin bis-thiomethylation in Aspergillus fumigatus.,Dolan SK, Bock T, Hering V, Owens RA, Jones GW, Blankenfeldt W, Doyle S Open Biol. 2017 Feb;7(2). pii: 160292. doi: 10.1098/rsob.160292. PMID:28179499 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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