Dec 5, 2014 · In this study we focus on a commonly observed type of DFG-out conformation, which we label “classical DFG-out”, where the D and the F of the DFG motif have swapped positions. We provide simple structural criteria for identifying “classical DFG-out” conformations and relate this information to the requirements for binding type II inhibitors.

Jul 23, 2015 · Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp–Phe–Gly (DFG) motif of the activation loop, with some, including FGFR1 kinase,...

Jun 20, 2013 · In this issue of Chemistry & Biology, Hari and colleagues show that two positions in kinase active sites, including the well-known “gatekeeper” residue, regulate “in” versus “out” conformations of the conserved “DFG” motif. These findings suggest yet another role for the gatekeeper residue.

Jun 20, 2013 · In this issue of Chemistry & Biology, Hari and colleagues show that two positions in kinase active sites, including the well-known "gatekeeper" residue, regulate "in" versus "out" conformations of the conserved "DFG" motif. These findings suggest yet another role for the gatekeeper residue.

Apr 8, 2011 · In the inactive, DFG-out conformation (PDB ID 1OPK), DFG-phenylalanine flips toward the active site. The DFG residues are indicated by single letter amino acid codes (D, F, G), as are the catalytic lysine (K), the catalytic glutamate in helix αC …

On the basis of a visual analysis of a few representative structures and subsequent k-means clustering employing an unsupervised approach, we labeled those conformations for which D1 < 7.2 Å and D2 > 9 Å as “classical DFG-out” conformations.

Jul 19, 2018 · We assess a range of structural features derived from the conserved αC helix and DFG motif to define the conformational space of the catalytic domain of protein kinases. We then construct Kinformation, a random forest classifier, to annotate the conformation of 3,708 kinase structures in the PDB.

Jan 8, 2015 · We have completed a structural analysis of almost 200 small molecule inhibitors bound to classical DFG-out conformations; we find that they are recognized by both type I and type II inhibitors. In contrast, we find that nonclassical DFG-out conformations strongly select against type II inhibitors because these structures have not formed a large ...

We have completed a structural analysis of almost 200 small molecule inhibitors bound to classical DFG-out conformations; we find that they are recognized by both type I and type II inhibitors.

Nov 24, 2014 · We first perform a comprehensive analysis of all protein kinase structures deposited in the Protein Data Bank. We then develop DFGmodel, a method that takes either a known structure of a kinase in the active conformation or a sequence of a kinase without a structure, to generate kinase models in the inactive conformation.