6siu
From Proteopedia
Crystal structure of IbpAFic2 covalently tethered to Cdc42
Structural highlights
FunctionIBPA_HISS2 Adenylyltransferase involved in virulence by mediating the addition of adenosine 5'-monophosphate (AMP) to specific tyrosine residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly in infected cells. Probably also acts as a cysteine protease, which may play a central role after invasion of host cell and in virulence. Possible member (with IbpB) of a 2 partner secretion. Probably able to bind bovine epithelial cells (host cells). May participate in the formation of fibrils at the surface of the bacteria.[1] [2] [3] [4] Publication Abstract from PubMedVarious pathogenic bacteria use post-translational modifications to manipulate the central components of host cell functions. Many of the enzymes released by these bacteria belong to the large Fic family, which modify targets with nucleotide monophosphates. The lack of a generic method for identifying the cellular targets of Fic family enzymes hinders investigation of their role and the effect of the post-translational modification. Here, we establish an approach that uses reactive co-substrate-linked enzymes for proteome profiling. We combine synthetic thiol-reactive nucleotide derivatives with recombinantly produced Fic enzymes containing strategically placed cysteines in their active sites to yield reactive binary probes for covalent substrate capture. The binary complexes capture their targets from cell lysates and permit subsequent identification. Furthermore, we determined the structures of low-affinity ternary enzyme-nucleotide-substrate complexes by applying a covalent-linking strategy. This approach thus allows target identification of the Fic enzymes from both bacteria and eukarya. Identification of targets of AMPylating Fic enzymes by co-substrate-mediated covalent capture.,Gulen B, Rosselin M, Fauser J, Albers MF, Pett C, Krisp C, Pogenberg V, Schluter H, Hedberg C, Itzen A Nat Chem. 2020 Aug;12(8):732-739. doi: 10.1038/s41557-020-0484-6. Epub 2020 Jul, 6. PMID:32632184[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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