KLIFS: A knowledge-based structural database to navigate kinase-ligand interaction space
Research output: Contribution to journal › Review › Research › peer-review
Standard
KLIFS : A knowledge-based structural database to navigate kinase-ligand interaction space. / Van Linden, Oscar P.J.; Kooistra, Albert J.; Leurs, Rob; De Esch, Iwan J.P.; De Graaf, Chris.
In: Journal of Medicinal Chemistry, Vol. 57, No. 2, 23.01.2014, p. 249-277.Research output: Contribution to journal › Review › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - KLIFS
T2 - A knowledge-based structural database to navigate kinase-ligand interaction space
AU - Van Linden, Oscar P.J.
AU - Kooistra, Albert J.
AU - Leurs, Rob
AU - De Esch, Iwan J.P.
AU - De Graaf, Chris
PY - 2014/1/23
Y1 - 2014/1/23
N2 - Protein kinases regulate the majority of signal transduction pathways in cells and have become important targets for the development of designer drugs. We present a systematic analysis of kinase-ligand interactions in all regions of the catalytic cleft of all 1252 human kinase-ligand cocrystal structures present in the Protein Data Bank (PDB). The kinase-ligand interaction fingerprints and structure database (KLIFS) contains a consistent alignment of 85 kinase ligand binding site residues that enables the identification of family specific interaction features and classification of ligands according to their binding modes. We illustrate how systematic mining of kinase-ligand interaction space gives new insights into how conserved and selective kinase interaction hot spots can accommodate the large diversity of chemical scaffolds in kinase ligands. These analyses lead to an improved understanding of the structural requirements of kinase binding that will be useful in ligand discovery and design studies.
AB - Protein kinases regulate the majority of signal transduction pathways in cells and have become important targets for the development of designer drugs. We present a systematic analysis of kinase-ligand interactions in all regions of the catalytic cleft of all 1252 human kinase-ligand cocrystal structures present in the Protein Data Bank (PDB). The kinase-ligand interaction fingerprints and structure database (KLIFS) contains a consistent alignment of 85 kinase ligand binding site residues that enables the identification of family specific interaction features and classification of ligands according to their binding modes. We illustrate how systematic mining of kinase-ligand interaction space gives new insights into how conserved and selective kinase interaction hot spots can accommodate the large diversity of chemical scaffolds in kinase ligands. These analyses lead to an improved understanding of the structural requirements of kinase binding that will be useful in ligand discovery and design studies.
UR - http://www.scopus.com/inward/record.url?scp=84893065058&partnerID=8YFLogxK
U2 - 10.1021/jm400378w
DO - 10.1021/jm400378w
M3 - Review
C2 - 23941661
AN - SCOPUS:84893065058
VL - 57
SP - 249
EP - 277
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 2
ER -
ID: 199376955