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| | <StructureSection load='6kl2' size='340' side='right'caption='[[6kl2]], [[Resolution|resolution]] 2.63Å' scene=''> | | <StructureSection load='6kl2' size='340' side='right'caption='[[6kl2]], [[Resolution|resolution]] 2.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kl2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mers Mers]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KL2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KL2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6kl2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KL2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KL2 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kl2 OCA], [http://pdbe.org/6kl2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kl2 RCSB], [http://www.ebi.ac.uk/pdbsum/6kl2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kl2 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.63Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6kl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kl2 OCA], [https://pdbe.org/6kl2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kl2 RCSB], [https://www.ebi.ac.uk/pdbsum/6kl2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kl2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A0D3MU65_9BETC A0A0D3MU65_9BETC]] 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.[SAAS:SAAS01160654] | + | [https://www.uniprot.org/uniprot/NCAP_MERS1 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] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6kl2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6kl2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mers]] | + | [[Category: Middle East respiratory syndrome-related coronavirus]] |
| - | [[Category: Hou, M H]] | + | [[Category: Hou MH]] |
| - | [[Category: Hsu, J N]] | + | [[Category: Hsu JN]] |
| - | [[Category: Lin, S M]] | + | [[Category: Lin SM]] |
| - | [[Category: Wang, Y S]] | + | [[Category: Wang YS]] |
| - | [[Category: Middle east respiratory syndrome coronavirus]]
| + | |
| - | [[Category: N-terminal domain]]
| + | |
| - | [[Category: Nucleocapsid protein]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin SM, Lin SC, Hsu JN, Chang CK, Chien CM, Wang YS, Wu HY, Jeng US, Kehn-Hall K, Hou MH. Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design. J Med Chem. 2020 Mar 11. doi: 10.1021/acs.jmedchem.9b01913. PMID:32105468 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01913
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