1ft2
From Proteopedia
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|PDB= 1ft2 |SIZE=350|CAPTION= <scene name='initialview01'>1ft2</scene>, resolution 3.40Å | |PDB= 1ft2 |SIZE=350|CAPTION= <scene name='initialview01'>1ft2</scene>, resolution 3.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= CDNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |GENE= CDNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ft2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ft2 OCA], [http://www.ebi.ac.uk/pdbsum/1ft2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ft2 RCSB]</span> | ||
}} | }} | ||
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[[Category: Casey, P J.]] | [[Category: Casey, P J.]] | ||
[[Category: Long, S B.]] | [[Category: Long, S B.]] | ||
| - | [[Category: FPP]] | ||
| - | [[Category: ZN]] | ||
[[Category: cancer therapeutic]] | [[Category: cancer therapeutic]] | ||
[[Category: farnesyl diphosphate]] | [[Category: farnesyl diphosphate]] | ||
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[[Category: protein farnesyltransferase]] | [[Category: protein farnesyltransferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:29:44 2008'' |
Revision as of 17:29, 30 March 2008
| |||||||
| , resolution 3.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | CDNA (Rattus norvegicus) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CO-CRYSTAL STRUCTURE OF PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A FARNESYL DIPHOSPHATE SUBSTRATE
Overview
Protein farnesyltransferase (FTase) catalyzes the transfer of the hydrophobic farnesyl group from farnesyl diphosphate (FPP) to cellular proteins such as Ras at a cysteine residue near their carboxy-terminus. This process is necessary for the subcellular localization of these proteins to the plasma membrane and is required for the transforming activity of oncogenic variants of Ras, making FTase a prime target for anticancer therapeutics. The high-resolution crystal structure of rat FTase was recently determined, and we present here the X-ray crystal structure of the first complex of FTase with a FPP substrate bound at the active site. The isoprenoid moiety of FPP binds in an extended conformation in a hydrophobic cavity of the beta subunit of the FTase enzyme, and the diphosphate moiety binds to a positively charged cleft at the top of this cavity near the subunit interface. The observed location of the FPP molecule is consistent with mutagenesis data. This binary complex of FTase with FPP leads us to suggest a "molecular ruler" hypothesis for isoprenoid substrate specificity, where the depth of the hydrophobic binding cavity acts as a ruler discriminating between isoprenoids of differing lengths. Although other length isoprenoids may bind in the cavity, only the 15-carbon farnesyl moiety binds with its C1 atom in register with a catalytic zinc ion as required for efficient transfer to the Ras substrate.
About this Structure
1FT2 is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate., Long SB, Casey PJ, Beese LS, Biochemistry. 1998 Jul 7;37(27):9612-8. PMID:9657673
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