8fj3

Crystal Structure of the Tick Evasin EVA-AAM1001 Complexed to Human Chemokine CCL7(Y13A)

spinqualitylabelsall models 8fj3, resolution 2.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fj3 is a 2 chain structure with sequence from Amblyomma americanum and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.07Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CCL7_HUMAN Chemotactic factor that attracts monocytes and eosinophils, but not neutrophils. Augments monocyte anti-tumor activity. Also induces the release of gelatinase B. This protein can bind heparin. Binds to CCR1, CCR2 and CCR3. Publication Abstract from PubMed Chemokines are key regulators of leukocyte trafficking and attractive targets for anti-inflammatory therapy. Evasins are chemokine-binding proteins from tick saliva, whose application as anti-inflammatory therapeutics will require manipulation of their chemokine target selectivity. Here we describe subclass A3 evasins, which are unique to the tick genus Amblyomma and distinguished from "classical" class A1 evasins by an additional disulfide bond near the chemokine recognition interface. The A3 evasin EVA-AAM1001 (EVA-A) bound to CC chemokines and inhibited their receptor activation. Unlike A1 evasins, EVA-A was not highly dependent on N- and C-terminal regions to differentiate chemokine targets. Structures of chemokine-bound EVA-A revealed a deep hydrophobic pocket, unique to A3 evasins, that interacts with the residue immediately following the CC motif of the chemokine. Mutations to this pocket altered the chemokine selectivity of EVA-A. Thus, class A3 evasins provide a suitable platform for engineering proteins with applications in research, diagnosis or anti-inflammatory therapy. Engineering broad-spectrum inhibitors of inflammatory chemokines from subclass A3 tick evasins.,Devkota SR, Aryal P, Pokhrel R, Jiao W, Perry A, Panjikar S, Payne RJ, Wilce MCJ, Bhusal RP, Stone MJ Nat Commun. 2023 Jul 14;14(1):4204. doi: 10.1038/s41467-023-39879-3. PMID:37452046 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monocyte chemoattractant protein

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