Grundlingern et al. show that Aspergillus fumigatus AFUA_3G03390 gene product, SidJ (aspfu-q4wf56) is involved in hydrolysis of siderophore fusarinine C. It is the first functionally characterized member of the family. Structure of siderophore esterase AfSidJ from Aspergillus fumigatus is described by Ecker et al.. A structure of a protein of unknown fucntion is also available (2Q0X) Merritt et al. . However this protein is only representative of trypanosomatid members of this sequence family as these proteins lack some if not all of the catalytic triad residues. Fusarinine C is an intracellular siderophore (an iron-chelating compound that transports iron across membranes) that is crucial for virulence. The closely related siderophore triacetylfusarinine C is not hydrolysed by SidJ. Homologues of SidJ are found in plants and bacteria. (Not to be cofounded with SidJ Calmodulin-dependent glutamylase from Legionella pneumophila).Previously named DUF_1749
Title: Iron Scavenging in Aspergillus Species: Structural and Biochemical Insights into Fungal Siderophore Esterases Ecker F, Haas H, Groll M, Huber EM Ref: Angew Chem Int Ed Engl, 57:14624, 2018 : PubMed
Fungi utilize high-affinity chelators termed siderophores with chemically diverse structures to scavenge the essential nutrient iron from their surroundings. Since they are among the strongest known Fe(3+) binding agents, intracellular release of the heavy metal atom is facilitated by the activity of specific hydrolases. In this work, we report the characterization and X-ray crystal structures of four siderophore esterases: AfEstB and AfSidJ from Aspergillus fumigatus, as well as AnEstB and AnEstA from Aspergillus nidulans. Even though they all display the conserved alpha/beta-hydrolase fold, we found significant structural and enzymatic discrepancies in their adaption to both related and chemically diverse substrates. A structure of AfEstB in complex with its substrate triacetylfusarinine C gives insight into the active enzyme and shows tetrahedral coordination between the catalytic serine and the scissile ester bond.
Siderophore-mediated iron handling is crucial for the virulence of Aspergillus fumigatus. Here we identified a new component of its siderophore metabolism, termed SidJ, which is encoded by AFUA_3G03390. The encoding gene is localized in a siderophore biosynthetic gene cluster that is conserved in a variety of fungi. During iron starvation, SidJ deficiency resulted in decreased growth and increased intracellular accumulation of hydrolysis products of the siderophore fusarinine C. The implied role in siderophore hydrolysis is consistent with a putative esterase domain in SidJ, which now represents the first functionally characterized member of the DUF1749 (domain of unknown function) protein family, with members found exclusively in fungi and plants.
The structure of a structural genomics target protein, Tbru020260AAA from Trypanosoma brucei, has been determined to a resolution of 2.2 A using multiple-wavelength anomalous diffraction at the Se K edge. This protein belongs to Pfam sequence family PF08538 and is only distantly related to previously studied members of the alpha/beta-hydrolase fold family. Structural superposition onto representative alpha/beta-hydrolase fold proteins of known function indicates that a possible catalytic nucleophile, Ser116 in the T. brucei protein, lies at the expected location. However, the present structure and by extension the other trypanosomatid members of this sequence family have neither sequence nor structural similarity at the location of other active-site residues typical for proteins with this fold. Together with the presence of an additional domain between strands beta6 and beta7 that is conserved in trypanosomatid genomes, this suggests that the function of these homologs has diverged from other members of the fold family.
Other Papers
No structure scheme yet for this family
Structures in Fusarinine_C_esterase_sidJ family (2)
