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Backbone Comparisons of the Tyrosine Kinase Domain of Fibroblast Growth Factor Receptor 1

The crystal structure of each molecule (the unbound Tyrosine Kinase region and this region bound to inhibitors PD-173074 or SU-4984 ) shows a unit cell dimer .(Kinemage 1). The backbones from crystal structures of the tyrosine kinase domain of FGFR 1 and the same region when bound to inhibitors PD-173074 and SU-4984 show no distinct differences.

The side chains, with the exception of Lys-514 (which moves to accommodate the incoming methoxy group of PD-173074), also appear relatively unchanged upon inhibitor binding to the tyrosine kinase domain of FGFR1. (Kinemage 2).

An overlay of unbound and both inhibitor-bound chains is shown in Kinemage 3.

The Kinemages

A single click on the KiNG logo will launch the kinemage. The number under the KiNG logo is the download size (in bytes).

Use the left mouse button to rotate the molecule.

If the KiNG logo is absent or the application does not launch, see Gray Box Error.

Kinemage 1: Dimer structures for inhibitor bound and unbound tyrosine kinase domain of FGFR 1

Image requires a Java enabled browser 102 K
Click On KiNG to see	Crystal Structure Dimers

Kinemage 2: Comparison of the inhibitor bound monomer (Chain A) to the unbound tyrosine kinase domain of FGFR 1

View 1  overlay of the three structures
View 2  arbitrary top view
View 3  arbitrary front view of the inhibitory binding cleft
View 4  bottom of the inhibitor binding cleft

Image requires a Java enabled browser 1,072 K
Click On KiNG to see	Monomer Showing Inhibitor Binding

Kinemage 3: Overlay of the Unbound and Both Inhibitor-Bound Tyrosine Kinase Chains

View 1  overlay of the three structures
View 2  arbitrary top view
View 3  arbitrary front view of the inhibitory binding cleft
View 4  bottom of the inhibitor binding cleft
View 5  bound and unbound position of Lys-514

Image requires a Java enabled browser 1,055 K
Click On KiNG to see	Three Structure Overlay

Sequence: (X-ray resolved residues are 465-762 of the human FGFR 1)

Unresolved N-Terminal: MVAGVSEYE

X-Ray Resolved: LPEDPRWELPRDRLVLGKPLGEGAFGQVVLAEAIGLDKDKP
NRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKNIINLLGACTQDGPLYVIVE
YASKGNLREYLQARRPPGLEYSYNPSHNPEEQLSSKDLVSCAYQVARGMEYLASKK
CIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVKWMAPEALFDR
IYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMM
MRDCWHAVPSQRPTFKQLVEDLDRIVALTS

Unresolved C-Terminal: NQE 

Source:

Human sequence expressed in spodoptera frugiperda insect cell line sf9; Structural coordinates were taken from the Brookhaven Database file 2FGI. Structural Coordinates from the Brookhaven Database files1AGM, 1FGK, and 2FGI.

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FGF Site: FGF Intro     Nomenclature     Notes     References     FGF Sequences     FGFR Sequences     Site Map

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Copyright 2005-2007 by Larry P. Taylor
Molecular & Behavioral Neuroscience Institute
University of Michigan

All Rights Reserved

Supported by the Pritzker Neuropsychiatric Disorders Research Consortium, and by NIH Grant 5 P01 MH42251, Conte Center Grant #L99MH60398, RO1 DA13386 and the Office of Naval Research (ONR) N00014-02-1-0879 to Huda Akil & Stanley J. Watson. at the Molecular & Behavioral Neuroscience Institute.