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7SO0

Crystal Structure of the Engineered Tick Evasin EVA-P974(F31A) Complexed to Human Chemokine CCL2

Summary for 7SO0
Entry DOI10.2210/pdb7so0/pdb
DescriptorEvasin P974, C-C motif chemokine 2 (3 entities in total)
Functional Keywordsinflammation, chemokine, tick evasin, immune system
Biological sourceAmblyomma cajennense (Cayenne tick, Acarus cajennensis)
More
Total number of polymer chains2
Total formula weight18298.99
Authors
Bhusal, R.P.,Devkota, S.R.,Aryal, P.,Wilce, M.C.J.,Stone, M.J. (deposition date: 2021-10-28, release date: 2022-03-16, Last modification date: 2024-10-23)
Primary citationBhusal, R.P.,Aryal, P.,Devkota, S.R.,Pokhrel, R.,Gunzburg, M.J.,Foster, S.R.,Lim, H.D.,Payne, R.J.,Wilce, M.C.J.,Stone, M.J.
Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases.
Proc.Natl.Acad.Sci.USA, 119:-, 2022
Cited by
PubMed Abstract: As natural chemokine inhibitors, evasin proteins produced in tick saliva are potential therapeutic agents for numerous inflammatory diseases. Engineering evasins to block the desired chemokines and avoid off-target side effects requires structural understanding of their target selectivity. Structures of the class A evasin EVA-P974 bound to human CC chemokine ligands 7 and 17 (CCL7 and CCL17) and to a CCL8-CCL7 chimera reveal that the specificity of class A evasins for chemokines of the CC subfamily is defined by conserved, rigid backbone-backbone interactions, whereas the preference for a subset of CC chemokines is controlled by side-chain interactions at four hotspots in flexible structural elements. Hotspot mutations alter target preference, enabling inhibition of selected chemokines. The structure of an engineered EVA-P974 bound to CCL2 reveals an underlying molecular mechanism of EVA-P974 target preference. These results provide a structure-based framework for engineering evasins as targeted antiinflammatory therapeutics.
PubMed: 35217625
DOI: 10.1073/pnas.2122105119
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.74 Å)
Structure validation

226707

數據於2024-10-30公開中

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