Farnesyltransferase, a subunit (FNTA)

Farnesyltransferase is one of the three enzymes in the prenyltransferase group. Specifically, farnesyltransferase (FTase) adds a 15 carbon isoprenoid called a farnesyl group to proteins bearing a CaaX motif: a four amino acid sequence at the carboxyl terminus of a protein. Farnesyltransferase's targets include members of the Ras superfamily of small GTP binding proteins critical to cell cycle progression. For this reason, several FTase inhibitors are undergoing testing as anti-cancer agents. FTase inhibitors have also shown efficacy as anti-parasitic agents as well. FTase is also believed to play an important role in development of progeria and various forms of cancers.\n\nFarnesyltransferase, posttranslationally modify proteins by adding an isoprenoid lipid called a farnesyl group to the carboxyl terminus of the target protein. This process, called farnesylation (more generally prenylation), causes farnesylated proteins to become membrane associated due to the hydrophobic nature of the farnesyl group. Most farnesylated proteins are involved in cellular signaling where membrane association is critical for function.\n[edit]Farnesyltransferase structure and function\n\nFarnesyltransferase has two subunits: a 48kD alpha subunit and a 46kD beta subunit. Both subunits are primarily composed of alpha helices. The a subunit is made of a double layer of paired alpha helices stacked in parallel which wraps partly around the beta subunit like a blanket. The alpha helices of the b subunit form a barrel. The active site is formed by the center of the b subunit flanked by part of the a subunit. Farnesyltransferase coordinates a zinc cation on its b subunit at the lip of the active site. Farnesyltransferase has a hydrophobic binding pocket for farnesyl diphosphate, the lipid donor molecule. All farnesyltransferase substrates invariably have a cysteine as their fourth to last residue. This cysteine engages in an SN2 type attack, coordinated by the zinc and a transient stabilizing magnesium ion on the farnesyl diphosphate, displacing the diphosphate. The product remains bound to farnesyltransferase until displaced by new substrates. The last three amino acids of the CaaX motif are removed later.\n\nThere are four binding pockets in FTase which accommodate the last four amino acids on the carboxyl-terminus of a protein. Only those with a suitable CaaX motif can bind. As stated above the fourth to last residue is always a cysteine. The other three residues may vary. The carboxyl-terminal amino acid (X) discriminates FTase

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SPECIFICATIONS

Catalog Number

F0019-58X1

Size

100ul

Applications

WB

Hosts

Mouse

Reactivities

Hum

Form

Supplied as a liquid in PBS with 0.1% sodium azide.

P Type

Mab

Purity

Purified by Protein A.

Isotype

IgG1

References

1. Delarue, F L, et al (2006). Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter.\n2. Lubet, Ronald A, et al (2006). Effects of the farnesyl transferase inhibitor R115777 (Zarnestra) on mammary carcinogenesis: prevention, therapy, and role of HaRas mutations. Mol Cancer Ther 5: 1073- 1078.\nGeneral References:\nReid, T. Scott, Terry, Kimberly L., Casey, Patrick J., Beese, Lorena S., (2004) Crystallographic Analysis of CaaX prenyltransferases Complexed with Substrates Defines Rules of Protein Substrate Selectivity, J. Mol. Bio, 343, 417-433.\nEastman, Richard T., Buckner, Frederick S., et al., (2006) Fighting parasitic disease by Blocking Protein Farnesylation, Journal of Lipid Research, 47, 233-240.\nBeese, Lorena, S., Lane, Kimberly T. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type 1. Journal of Lipid Research, 47, 68

Additional Info

Specific to the alpha subunit of farnesyl transferase.