5e7x

Ligand binding domain 1 of Penicillium marneffei MP1 protein in complex with palmitic acid

spinqualitylabelsall models 5e7x, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5e7x is a 1 chain structure with sequence from Talaromyces marneffei PM1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: ACT, GOL, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A8HBN5_TALMA Publication Abstract from PubMed Talaromyces marneffei (T. marneffei) infection causes talaromycosis (previously known as penicilliosis), the second most-deadly opportunistic systematic mycosis in immuno-compromised patients. Different virulence mechanisms in T. marneffei had been proposed and investigated. In the sera of patients with talaromycosis, Mp1 protein (Mp1p), a secretory galactomannoprotein antigen encoding two tandem ligand-binding domains (Mp1p-LBD1 and Mp1p-LBD2), was found to be abundant. Mp1p-LBD2 was reported to possess a hydrophobic cavity to bind co-purified palmitic acid (PLM). It was hypothesized that capturing of lipids from human hosts by expressing large quantity of Mp1p may be a possible virulence mechanism of T. marneffei. It was shown that expression of Mp1p enhanced the intracellular survival of T. marneffei by suppressing pro-inflammatory responses. Mechanistic study of Mp1p-LBD2 suggested that arachidonic acid (AA), precursor of paracrine signaling molecules for regulations of inflammatory responses, is the major physiological target of Mp1p-LBD2. In this study, we use crystallographic and biochemical techniques to further demonstrate that Mp1p-LBD1, the previously unsolved first lipid binding domain of Mp1p, is also a strong AA-binding domain in Mp1p. These studies on Mp1p-LBD1 support that the highly-expressed Mp1p is an effective AA-capturing protein. Each Mp1p can bind up to 4 AA molecules. The crystal structure of Mp1p-LBD1-LBD2 has also been solved, showing that both LBDs are likely to function independently with a flexible linker in between. T. marneffei and potentially other pathogens highly expressing and secreting proteins similar to Mp1p can severely disturb hosts' signaling cascades during pro-inflammatory responses, by reducing the availabilities of important paracrine signaling molecules. Talaromyces marneffei Mp1 protein, a novel virulence factor, carries two arachidonic acid-binding domains to suppress inflammatory responses in hosts.,Lam WH, Sze KH, Ke Y, Tse MK, Zhang H, Woo PCY, Lau SKP, Lau CCY, Xu S, Lai PM, Zhou T, Antonyuk SV, Kao RYT, Yuen KY, Hao Q Infect Immun. 2019 Jan 22. pii: IAI.00679-18. doi: 10.1128/IAI.00679-18. PMID:30670555 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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