5J40: The X-ray Structure Of Jcv Helicase

Citation:
Abstract
There are currently no treatments for life-threatening infections caused by human polyomaviruses JCV and BKV. We therefore report herein the first crystal structure of the hexameric helicase of JCV large T antigen (apo) and its use to drive the structure-based design of dual JCV and BKV ATP-competitive inhibitors. The crystal structures obtained by soaking our early inhibitors into the JCV helicase allowed us to rapidly improve the biochemical activity of our inhibitors from 18 muM for the early 6-(2-methoxyphenyl)- and the 6-(2-ethoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole hits 1a and 1b to 0.6 muM for triazolopyridine 12i. In addition, we were able to demonstrate measurable antiviral activity in Vero cells for our thiazolopyridine series in the absence of marked cytotoxicity, thus confirming the usefulness of this approach.
PDB ID: 5J40Download
MMDB ID: 140803
PDB Deposition Date: 2016/3/31
Updated in MMDB: 2016/08
Experimental Method:
x-ray diffraction
Resolution: 2.17  Å
Source Organism:
Similar Structures:
Biological Unit for 5J40: hexameric; determined by author and by software (PISA)
Molecular Components in 5J40
Label Count Molecule
Proteins (6 molecules)
6
Large T Antigen(Gene symbol: Jvgp5)
Molecule annotation
Chemicals (18 molecules)
1
6
2
6
3
6
* Click molecule labels to explore molecular sequence information.

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