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Functions of metals in protein farnesyltransferase

Publication ,  Journal Article
Huang, CC; Casey, PJ; Fierke, CA
Published in: FASEB Journal
1997

Mammalian protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the addition of a farnesyl isoprenoid to a conserved cysteine in peptide or protein substrates. In addition to zinc, FTase also requires mM concentrations of magnesium for optimal reactivity. In order to further understand the catalytic roles of these two metals in l,'Tase, we have used metal-substituted enzymes in combination with transient kinetic experiments to directly measure the catalytic step. Metal coordination of the peptide thiot is indicated by observation of a metal-sulfur charge transfer band in the absorption spectrum of cobalt-substituted FrI'ase ternary complexes. Additionally. the rate constant of product formation of (admium-substituted FTase is similar to that ofzinc-FTase. Using the zinc-enzyme with two peptide substrates, GCVLS and CVIM, derived from H-Ras and KRas, respectively, we have found that product can be formed in the absence of magnesium although the rate constant is decreased. In addition, the ('VIM substrate has a decreased requirement for magnesium. The combination of detailed kinetic and thermodynamic analysis with metal substitution experiments provides insights into the mechanism of protein prenyl transferases. (supported by NItt GM 40602).

Duke Scholars

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1997

Volume

11

Issue

9

Start / End Page

A1307

Related Subject Headings

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

Citation

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MLA
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Huang, C. C., Casey, P. J., & Fierke, C. A. (1997). Functions of metals in protein farnesyltransferase. FASEB Journal, 11(9), A1307.
Huang, C. C., P. J. Casey, and C. A. Fierke. “Functions of metals in protein farnesyltransferase.” FASEB Journal 11, no. 9 (1997): A1307.
Huang CC, Casey PJ, Fierke CA. Functions of metals in protein farnesyltransferase. FASEB Journal. 1997;11(9):A1307.
Huang, C. C., et al. “Functions of metals in protein farnesyltransferase.” FASEB Journal, vol. 11, no. 9, 1997, p. A1307.
Huang CC, Casey PJ, Fierke CA. Functions of metals in protein farnesyltransferase. FASEB Journal. 1997;11(9):A1307.

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1997

Volume

11

Issue

9

Start / End Page

A1307

Related Subject Headings

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