6xft | pdb_00006xft

Crystal Structure of the Cys-NO Modified YopH Tyrosine Phosphatase

spinqualitylabelsall models 6xft, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6xft is a 1 chain structure with sequence from "bacterium_enterocoliticum"_schleifstein_and_coleman_1939 "bacterium enterocoliticum" schleifstein and coleman 1939. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: SNC Gene: yopH, yop51 ("Bacterium enterocoliticum" Schleifstein and Coleman 1939) Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [YOPH_YEREN] Essential virulence determinant. This protein is a protein tyrosine phosphatase. The essential function of YopH in Yersinia pathogenesis is host-protein dephosphorylation. It contributes to the ability of the bacteria to resist phagocytosis by peritoneal macrophages. Publication Abstract from PubMed Protein tyrosine phosphatases (PTPs) are key virulence factors in pathogenic bacteria, consequently, they have become important targets for new approaches against these pathogens, especially in the fight against antibiotic resistance. Among these targets of interest YopH (Yersinia outer protein H) from virulent species of Yersinia is an example. PTPs can be reversibly inhibited by nitric oxide (NO) since the oxidative modification of cysteine residues may influence the protein structure and catalytic activity. We therefore investigated the effects of NO on the structure and enzymatic activity of Yersinia enterocolitica YopH in vitro. Through phosphatase activity assays, we observe that in the presence of NO YopH activity was inhibited by 50%, and that this oxidative modification is partially reversible in the presence of DTT. Furthermore, YopH S-nitrosylation was clearly confirmed by a biotin switch assay, high resolution mass spectrometry (MS) and X-ray crystallography approaches. The crystal structure confirmed the S-nitrosylation of the catalytic cysteine residue, Cys403, while the MS data provide evidence that Cys221 and Cys234 might also be modified by NO. Interestingly, circular dichroism spectroscopy shows that the S-nitrosylation affects secondary structure of wild type YopH, though to a lesser extent on the catalytic cysteine to serine YopH mutant. The data obtained demonstrate that S-nitrosylation inhibits the catalytic activity of YopH, with effects beyond the catalytic cysteine. These findings are helpful for designing effective YopH inhibitors and potential therapeutic strategies to fight this pathogen or others that use similar mechanisms to interfere in the signal transduction pathways of their hosts. Crystal structure of the Cys-NO modified YopH tyrosine phosphatase.,Rocha RF, Martins PGA, D'Muniz Pereira H, Brandao-Neto J, Thiemann OH, Terenzi H, Menegatti ACO Biochim Biophys Acta Proteins Proteom. 2022 Jan 5;1870(3):140754. doi:, 10.1016/j.bbapap.2022.140754. PMID:34995802 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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