5F41
DENGUE SEROTYPE 3 RNA-DEPENDENT RNA POLYMERASE BOUND TO FD-83-KI26
Summary for 5F41
| Entry DOI | 10.2210/pdb5f41/pdb |
| Related | 5F3Z 5FST |
| Descriptor | Genome polyprotein, ZINC ION, 2-(4-methoxy-3-thiophen-3-yl-phenyl)ethanoic acid, ... (4 entities in total) |
| Functional Keywords | inhibitor rdrp, dengue virus, transferase |
| Biological source | Dengue virus 3 |
| Cellular location | Virion membrane ; Multi-pass membrane protein : Q6DLV0 |
| Total number of polymer chains | 1 |
| Total formula weight | 74003.98 |
| Authors | Noble, C.G. (deposition date: 2015-12-03, release date: 2016-02-24, Last modification date: 2023-11-08) |
| Primary citation | Noble, C.G.,Lim, S.P.,Arora, R.,Yokokawa, F.,Nilar, S.,Seh, C.C.,Wright, S.K.,Benson, T.E.,Smith, P.W.,Shi, P.Y. A Conserved Pocket in the Dengue Virus Polymerase Identified through Fragment-based Screening J.Biol.Chem., 291:8541-8548, 2016 Cited by PubMed Abstract: We performed a fragment screen on the dengue virus serotype 3 RNA-dependent RNA polymerase using x-ray crystallography. A screen of 1,400 fragments in pools of eight identified a single hit that bound in a novel pocket in the protein. This pocket is located in the polymerase palm subdomain and conserved across the four serotypes of dengue virus. The compound binds to the polymerase in solution as evidenced by surface plasmon resonance and isothermal titration calorimetry analyses. Related compounds where a phenyl is replaced by a thiophene show higher affinity binding, indicating the potential for rational design. Importantly, inhibition of enzyme activity correlated with the binding affinity, showing that the pocket is functionally important for polymerase activity. This fragment is an excellent starting point for optimization through rational structure-based design. PubMed: 26872970DOI: 10.1074/jbc.M115.710731 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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