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| | ==Structure of FPT bound to DATFP-DH-GPP== | | ==Structure of FPT bound to DATFP-DH-GPP== |
| - | <StructureSection load='3ksl' size='340' side='right' caption='[[3ksl]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='3ksl' size='340' side='right'caption='[[3ksl]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ksl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KSL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KSL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ksl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KSL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SZH:(2S,6E)-8-{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]OXY}-2,6-DIMETHYLOCT-6-EN-1-YL+(2S)-3,3,3-TRIFLUORO-2-HYDRAZINOPROPANOATE'>SZH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fnta ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Fntb ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SZH:(2S,6E)-8-{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]OXY}-2,6-DIMETHYLOCT-6-EN-1-YL+(2S)-3,3,3-TRIFLUORO-2-HYDRAZINOPROPANOATE'>SZH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_farnesyltransferase Protein farnesyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.58 2.5.1.58] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ksl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ksl OCA], [https://pdbe.org/3ksl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ksl RCSB], [https://www.ebi.ac.uk/pdbsum/3ksl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ksl ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ksl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ksl OCA], [http://pdbe.org/3ksl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ksl RCSB], [http://www.ebi.ac.uk/pdbsum/3ksl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ksl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FNTB_RAT FNTB_RAT]] Catalyzes the transfer of a farnesyl moiety from farnesyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins. The beta subunit is responsible for peptide-binding. | + | [https://www.uniprot.org/uniprot/FNTA_RAT FNTA_RAT] Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. The alpha subunit is thought to participate in a stable complex with the substrate. The beta subunit binds the peptide substrate. Through RAC1 prenylation and activation may positively regulate neuromuscular junction development downstream of MUSK (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Farnesyltransferase|Farnesyltransferase]] | + | *[[Farnesyltransferase 3D structures|Farnesyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Protein farnesyltransferase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: DeGraw, A]] | + | [[Category: DeGraw A]] |
| - | [[Category: Distefano, M D]] | + | [[Category: Distefano MD]] |
| - | [[Category: Edelstein, R L]] | + | [[Category: Edelstein RL]] |
| - | [[Category: Henry, O]] | + | [[Category: Henry O]] |
| - | [[Category: Hovlid, M L]] | + | [[Category: Hovlid ML]] |
| - | [[Category: Hruza, A W]] | + | [[Category: Hruza AW]] |
| - | [[Category: Labello, N P]] | + | [[Category: Labello NP]] |
| - | [[Category: Lenevich, S]] | + | [[Category: Lenevich S]] |
| - | [[Category: Lopez-Gallego, F]] | + | [[Category: Lopez-Gallego F]] |
| - | [[Category: Ochocki, J]] | + | [[Category: Ochocki J]] |
| - | [[Category: Schmidt-Dannert, C]] | + | [[Category: Schmidt-Dannert C]] |
| - | [[Category: Strickland, C L]] | + | [[Category: Strickland CL]] |
| - | [[Category: Talbot, T]] | + | [[Category: Talbot T]] |
| - | [[Category: Young, V]] | + | [[Category: Young V]] |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Prenyltransferase]]
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| - | [[Category: Transferase]]
| + | |
| - | [[Category: Zinc]]
| + | |
| Structural highlights
Function
FNTA_RAT Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. The alpha subunit is thought to participate in a stable complex with the substrate. The beta subunit binds the peptide substrate. Through RAC1 prenylation and activation may positively regulate neuromuscular junction development downstream of MUSK (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Photoactive analogs of farnesyl diphosphate (FPP) are useful probes in studies of enzymes that employ this molecule as a substrate. Here, we describe the preparation and properties of two new FPP analogs that contain diazotrifluoropropanoyl photophores linked to geranyl diphosphate via amide or ester linkages. The amide-linked analog (3) was synthesized in 32P-labeled form from geraniol in seven steps. Experiments with Saccharomyces cerevisiae protein farnesyltransferase (ScPFTase) showed that 3 is an alternative substrate for the enzyme. Photolysis experiments with [(32)P]3 demonstrate that this compound labels the beta-subunits of both farnesyltransferase and geranylgeranyltransferase (types 1 and 2). However, the amide-linked probe 3 undergoes a rearrangement to a photochemically unreactive isomeric triazolone upon long term storage making it inconvenient to use. To address this stability issue, the ester-linked analog 4 was prepared in six steps from geraniol. Computational analysis and X-ray crystallographic studies suggest that 4 binds to protein farnesyl transferase (PFTase) in a similar fashion as FPP. Compound 4 is also an alternative substrate for PFTase, and a 32P-labeled form selectively photocrosslinks the beta-subunit of ScPFTase as well as E. coli farnesyldiphosphate synthase and a germacrene-producing sesquiterpene synthase from Nostoc sp. strain PCC7120 (a cyanobacterial source). Finally, nearly exclusive labeling of ScPFTase in crude E. coli extract was observed, suggesting that [32P]4 manifests significant selectivity and should hence be useful for identifying novel FPP-utilizing enzymes in crude protein preparations.
Synthesis, properties, and applications of diazotrifluropropanoyl-containing photoactive analogs of farnesyl diphosphate containing modified linkages for enhanced stability.,Hovlid ML, Edelstein RL, Henry O, Ochocki J, DeGraw A, Lenevich S, Talbot T, Young VG, Hruza AW, Lopez-Gallego F, Labello NP, Strickland CL, Schmidt-Dannert C, Distefano MD Chem Biol Drug Des. 2010 Jan;75(1):51-67. PMID:19954434[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hovlid ML, Edelstein RL, Henry O, Ochocki J, DeGraw A, Lenevich S, Talbot T, Young VG, Hruza AW, Lopez-Gallego F, Labello NP, Strickland CL, Schmidt-Dannert C, Distefano MD. Synthesis, properties, and applications of diazotrifluropropanoyl-containing photoactive analogs of farnesyl diphosphate containing modified linkages for enhanced stability. Chem Biol Drug Des. 2010 Jan;75(1):51-67. PMID:19954434 doi:10.1111/j.1747-0285.2009.00914.x
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