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3e37

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Revision as of 21:50, 2 December 2018

Protein farnesyltransferase complexed with bisubstrate ethylenediamine scaffold inhibitor 5

Structural highlights

3e37 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1sa4, 1sa5, 2iej, 1kzo, 1kzp, 1d8d, 3e30, 3e32, 3e33, 3e34
Gene:	FNTA (HUMAN), FNTB (HUMAN)
Activity:	Protein farnesyltransferase, with EC number 2.5.1.58
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FNTA_HUMAN] 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). [FNTB_HUMAN] 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.

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

Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of anticancer therapeutics and, more recently, for the treatment of parasitic diseases caused by protozoan pathogens, including malaria (Plasmodium falciparum). We present the X-ray crystallographic structures of complexes of mammalian FTase with five inhibitors based on an ethylenediamine scaffold, two of which exhibit over 1000-fold selective inhibition of P. falciparum FTase. These structures reveal the dominant determinants in both the inhibitor and enzyme that control binding and selectivity. Comparison to a homology model constructed for the P. falciparum FTase suggests opportunities for further improving selectivity of a new generation of antimalarial inhibitors.

Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase.,Hast MA, Fletcher S, Cummings CG, Pusateri EE, Blaskovich MA, Rivas K, Gelb MH, Van Voorhis WC, Sebti SM, Hamilton AD, Beese LS Chem Biol. 2009 Feb 27;16(2):181-92. PMID:19246009^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hast MA, Fletcher S, Cummings CG, Pusateri EE, Blaskovich MA, Rivas K, Gelb MH, Van Voorhis WC, Sebti SM, Hamilton AD, Beese LS. Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase. Chem Biol. 2009 Feb 27;16(2):181-92. PMID:19246009 doi:10.1016/j.chembiol.2009.01.014

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3e37"

@@ Line 1: / Line 1: @@
 ==Protein farnesyltransferase complexed with bisubstrate ethylenediamine scaffold inhibitor 5==
 <StructureSection load='3e37' size='340' side='right' caption='[[3e37]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <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=9606 HUMAN]), FNTB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3e37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e37 OCA], [http://pdbe.org/3e37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e37 RCSB], [http://www.ebi.ac.uk/pdbsum/3e37 PDBsum]</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=3e37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e37 OCA], [http://pdbe.org/3e37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e37 RCSB], [http://www.ebi.ac.uk/pdbsum/3e37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3e37 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e3/3e37_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e3/3e37_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 51: / Line 52: @@
 [[Category: Prenyltransferase]]
 [[Category: Transferase]]
+[[Category: Zinc]]

3e37

From Proteopedia

Revision as of 21:50, 2 December 2018

Protein farnesyltransferase complexed with bisubstrate ethylenediamine scaffold inhibitor 5

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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