Skip to main content

Substrate binding is required for release of product from mammalian protein farnesyltransferase

Publication ,  Journal Article
Tschantz, WR; Furfine, ES; Casey, PJ
Published in: FASEB Journal
1997

Protein farnesyltransferase (FTase) catalyzes the modification by a farnesyl lipid of Ras and several other key proteins involved in cellular regulation. Previous studies on this important enzyme have indicated that product dissociation is the rate-limiting step in catalysis. A detailed examination of this has now been performed, and the results provide surprising insights into the mechanism of the enzyme. Examination of the binding of a farnesylated peptide product to free enzyme revealed a binding affinity of 1 #M. However, analysis of the product release step under single turnover conditions led to the surprising observation that the peptide product did not dissociate from the enzyme unless additional substrate was provided. Once additional substrate was provided, the enzyme released the farnesylated peptide product with rates comparable to the that of the overall catalysis by FTase. Additionally, stable FTase:farnesylated product complexes were formed using Ras proteins as substrates, and these complexes also require additional substrate for product release. These data have major implications in both our understanding of the overall mechanism of this enzyme and in design of inhibitors against this therapeutic target.

Duke Scholars

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1997

Volume

11

Issue

9

Start / End Page

A1086

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tschantz, W. R., Furfine, E. S., & Casey, P. J. (1997). Substrate binding is required for release of product from mammalian protein farnesyltransferase. FASEB Journal, 11(9), A1086.
Tschantz, W. R., E. S. Furfine, and P. J. Casey. “Substrate binding is required for release of product from mammalian protein farnesyltransferase.” FASEB Journal 11, no. 9 (1997): A1086.
Tschantz WR, Furfine ES, Casey PJ. Substrate binding is required for release of product from mammalian protein farnesyltransferase. FASEB Journal. 1997;11(9):A1086.
Tschantz, W. R., et al. “Substrate binding is required for release of product from mammalian protein farnesyltransferase.” FASEB Journal, vol. 11, no. 9, 1997, p. A1086.
Tschantz WR, Furfine ES, Casey PJ. Substrate binding is required for release of product from mammalian protein farnesyltransferase. FASEB Journal. 1997;11(9):A1086.

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1997

Volume

11

Issue

9

Start / End Page

A1086

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology