3VHK: Crystal Structure Of The Vegfr2 Kinase Domain In Complex With A Back Pocket Binder

Citation:
Abstract
We present a straightforward process for the discovery of novel back pocket-binding fragment molecules against protein tyrosine kinases. The approach begins by screening against the nonphosphorylated target kinase with subsequent counterscreening of hits against the phosphorylated enzyme. Back pocket-binding fragments are inactive against the phosphorylated kinase. Fragment molecules are of insufficient size to span both regions of the ATP binding pocket; thus, the outcome is binary (back pocket-binding or hinge-binding). Next, fragments with the appropriate binding profile are assayed in combination with a known hinge-binding fragment and subsequently with a known back pocket-binding fragment. Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses candidate fragments to crystallization trials. The method is exemplified by a fragment screening campaign against vascular endothelial growth factor receptor 2, and a novel back pocket-binding fragment is presented.
PDB ID: 3VHKDownload
MMDB ID: 102679
PDB Deposition Date: 2011/8/25
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 2.49  Å
Source Organism:
Similar Structures:
Biological Unit for 3VHK: monomeric; determined by author and by software (PISA)
Molecular Components in 3VHK
Label Count Molecule
Protein (1 molecule)
1
Vascular Endothelial Growth Factor Receptor 2(Gene symbol: KDR)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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