A Mutant Human Fibroblast Growth Factor 1

by

Larry P. Taylor, Ph. D.

 

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Email: lpt

Molecular & Behavioral Neuroscience Institute

The University of Michigan

Ann Arbor, MI

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

A Mutant Human Fibroblast Growth Factor 1

 

Growth factors represent a family of at least 18 proteins with a beta trefoil (three-fold repeat of a four-stranded sheet assembly without extended alpha helix strands) motif associated with cell proliferation and differentiation. They are a prime component of angiogenesis associated with organogenesis, tumor growth, and wound healing. The characteristics of the unit cell for this structure are summarized at pdbsum.

 

The human  FGF 1 structure and its receptor interactions are described on a separate page. This page highlights nmr studies on a mutant form of FGF 1. The experiment produced 24 different conformations.  (The Calpha trace for all 24 species is shown below left). The multiple structures are also shown in Kinemage 1. Clicking on the FGF 1 cartoon (below right) will launch a shockwave animation (requires shockwave browser plug-in) which uses these 24 structures to simulate the molecular dynamics of the FGF 1 molecule.

 

Calpha trace for 24 Confomers

 FGF 1 Cartoon Rendering

 

The overlay of multiple conformations highlights the most flexible areas of the molecule. The mutant FGF 1 species is also displayed as  ribbon (Kinemage 2 ) and a secondary structure cartoon ( Kinemage 3).

 

The Kinemages:

The real-time visualization using KiNG of the structures on this site requires a java-enabled (JRE from Java) browser. 

 

Possible Icons to the left of molecular model image on the download page

 

Java Not Activated Java Not Activated Java Functional
Blank Area

or message:

Image requires a Java enabled browser

 

KiNG Inactive KiNG Inactive KiNG Full Functional

 

A single click on the KiNG logo will launch the appropriate kinemage.

Kinemage 1: FGF 1 Conformations

Use the Animation Button to toggle through the  24 different conformations of this mutant FGF 1. Doing this rapidly provides a sense of the dynamics of the molecule.

 



Image requires a Java enabled browser

890 K

Click on KiNG to see FGF 1 Conformations


Kinemage 2: FGF 1 Ribbon Rendering

 



Image requires a Java enabled browser

200 K

Click on KiNG to see FGF 1


  Kinemage 3:  FGF 1 Cartoon Rendering

 



Image requires a Java enabled browser

 150 K

Click on KiNG to see    FGF 1 Cartoon

 

Sequence: (Human FGF 1, residues 28-154 of human sequence with AAA Added N-terminus)

AAALLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERL
EENHYNTYISKKHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPLPVSSD

This engineered protein replaced human residues 24,25,26 with Ala and Leu for Met-27.

Source:

 

The engineered expression vector (pMG624A) was expressed in Escherichia coli AB 1899. The structural coordinates were taken from Brookhaven Database File 1DZC,


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

 My University Home   Harris Links     Chemistry / Modeling Links


Copyright 2005-2020 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.