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Heparin Structure and Interactions with Basic Fibroblast Growth Factor

Faham, S. and Hileman, R. E. and Fromm, J. R. and Linhard, R. J. and Rees, D. C. (1996) Heparin Structure and Interactions with Basic Fibroblast Growth Factor. Science, 271 (5252). pp. 1116-1120. ISSN 0036-8075. https://resolver.caltech.edu/CaltechAUTHORS:20141223-090448077

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Abstract

Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174° and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135; the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.271.5252.1116 DOIArticle
http://www.sciencemag.org/content/271/5252/1116PublisherArticle
http://www.jstor.org/stable/2889846JSTORArticle
ORCID:
AuthorORCID
Rees, D. C.0000-0003-4073-1185
Additional Information:© 1996 American Association for the Advancement of Science. 19 September 1995; Accepted 12 December 1995. We thank T. Arakawa and G. M. Fox of Amgen for discussions and a generous supply of bFGF and D. Bar-Shalom for stimulating conversations. This work was funded in part by a gift from Amgen and U.S. Public Health Service (USPHS) grant GM38060(R.J.L.), with partial support of the x-ray facility provided by the Beckman Institute at California Institute of Technology and USPHS grant GM45162 (D.C.R.). S.F. was supported by USPHS Biotechnology Training grant T32 GM08346.
Funders:
Funding AgencyGrant Number
AmgenUNSPECIFIED
U.S. Public Health Service (USPHS)GM38060
Caltech Beckman Institute UNSPECIFIED
NIHGM45162
NIHT32 GM08346
Issue or Number:5252
Record Number:CaltechAUTHORS:20141223-090448077
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141223-090448077
Official Citation:Faham, S., Hileman, R. E., Fromm, J. R., Linhardt, R. J., & Rees, D. C. (1996). Heparin Structure and Interactions with Basic Fibroblast Growth Factor. Science, 271(5252), 1116-1120. doi: 10.1126/science.271.5252.1116
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53136
Collection:CaltechAUTHORS
Deposited By: Joanne McCole
Deposited On:23 Dec 2014 19:19
Last Modified:03 Oct 2019 07:47

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