8f5x

Crystal structure of human eosinophil-derived neurotoxin (EDN, ribonuclease 2) in complex with 5'-adenosine monophosphate (AMP)

spinqualitylabelsall models 8f5x, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8f5x is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: AMP, EDO, SIN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RNAS2_HUMAN This is a non-secretory ribonuclease. It is a pyrimidine specific nuclease with a slight preference for U. Cytotoxin and helminthotoxin. Selectively chemotactic for dendritic cells. Possesses a wide variety of biological activities. Publication Abstract from PubMed Evolutionarily conserved structural folds can give rise to diverse biological functions, yet predicting atomic-scale interactions that contribute to the emergence of novel activities within such folds remains challenging. Pancreatic-type ribonucleases illustrate this complexity, sharing a core structure that has evolved to accommodate varied functions. In this study, we used ancestral sequence reconstruction to probe evolutionary and molecular determinants that distinguish biological activities within eosinophil members of the RNase 2/3 subfamily. Our investigation unveils functional, structural, and dynamical behaviors that differentiate the evolved ancestral ribonuclease (AncRNase) from its contemporary eosinophil RNase orthologs. Leveraging the potential of ancestral reconstruction for protein engineering, we used AncRNase predictions to design a minimal 4-residue variant that transforms human RNase 2 into a chimeric enzyme endowed with the antimicrobial and cytotoxic activities of RNase 3 members. This work provides unique insights into mutational and evolutionary pathways governing structure, function, and conformational states within the eosinophil RNase subfamily, offering potential for targeted modulation of RNase-associated functions. Ancestral sequence reconstruction dissects structural and functional differences among eosinophil ribonucleases.,Tran TTQ, Narayanan C, Loes AN, Click TH, Pham NTH, Letourneau M, Harms MJ, Calmettes C, Agarwal PK, Doucet N J Biol Chem. 2024 Apr 7;300(5):107280. doi: 10.1016/j.jbc.2024.107280. PMID:38588810 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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