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5F41

DENGUE SEROTYPE 3 RNA-DEPENDENT RNA POLYMERASE BOUND TO FD-83-KI26

Summary for 5F41
Entry DOI10.2210/pdb5f41/pdb
Related5F3Z 5FST
DescriptorGenome polyprotein, ZINC ION, 2-(4-methoxy-3-thiophen-3-yl-phenyl)ethanoic acid, ... (4 entities in total)
Functional Keywordsinhibitor rdrp, dengue virus, transferase
Biological sourceDengue virus 3
Cellular locationVirion membrane ; Multi-pass membrane protein : Q6DLV0
Total number of polymer chains1
Total formula weight74003.98
Authors
Noble, C.G. (deposition date: 2015-12-03, release date: 2016-02-24, Last modification date: 2023-11-08)
Primary citationNoble, 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: 26872970
DOI: 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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