6kl5

Structure of The N-terminal domain of Middle East respiratory syndrome coronavirus Nucleocapsid Protein complexed with Benzyl 2-(Hydroxymethyl)-1-Indolinecarboxylate

spinqualitylabelsall models 6kl5, resolution 3.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kl5 is a 4 chain structure with sequence from Middle East respiratory syndrome-related coronavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.09Å Ligands: DJO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NCAP_MERS1 Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication.[HAMAP-Rule:MF_04096] Publication Abstract from PubMed Structure-based stabilization of protein-protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs, and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases. Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design.,Lin SM, Lin SC, Hsu JN, Chang CK, Chien CM, Wang YS, Wu HY, Jeng US, Kehn-Hall K, Hou MH J Med Chem. 2020 Mar 11. doi: 10.1021/acs.jmedchem.9b01913. PMID:32105468 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoprotein 3D structures

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