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6b07

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Revision as of 14:29, 4 October 2023

Crystal structure of CfFPPS2, a lepidopteran type-II farnesyl diphosphate synthase, complexed with [1-phosphono-2-(1-propylpyridin-2-yl)ethyl]phosphonic acid (inhibitor 1d)

Structural highlights

6b07 is a 3 chain structure with sequence from Choristoneura fumiferana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.98Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q1XAB1_CHOFU

Publication Abstract from PubMed

Farnesyl diphosphate synthase (FPPS) is an enzyme from the class of short chain (E)-prenyltransferases that catalyzes the condensation of two molecules of isopentenyl diphosphate (IPP, C5) with dimethylallyl diphosphate (DMAPP, C5) to generate the C15 product FPP. In insects, FPPS plays a key role in the biosynthesis of the morphogenetic and gonadotropic "juvenile hormone" (JH). Lepidopteran genomes encode two very distinct FPPS paralogs, one of which ("type-II") is expressed almost exclusively in the JH-producing glands, the corpora allata. This paralog has been hypothesized to display structural features that enable the binding of the bulkier precursors required for the biosynthesis of lepidopteran ethyl-branched JHs. Here, we report on the first crystal structures of an insect FPPS solved to date. Apo, ligand-bound, and inhibitor-bound structures of type-II FPPS (FPPS2) from the spruce budworm, Choristoneura fumiferana (Order: Lepidoptera), were obtained. Comparison of apo and inhibitor-bound enzymes revealed differences in both inhibitor binding and structural plasticity of CfFPPS2 compared to other FPPSs. Our data showed that IPP is not essential to the closure of the C-terminal tail. Ortho-substituted pyridinium bisphosphonates, previously shown to inhibit CfFPPS2, bound to the allylic site, as predicted; however, their alkyl groups were oriented towards the homoallylic binding site, with the bulkier propyl-substituted inhibitor penetrating deeply into the IPP binding pocket. The current study sheds light on the structural basis of substrate specificity of type-II FPPS of the spruce budworm. Through a comparison with other inhibitor-bound FPPSs, we propose several approaches to improve inhibitor selectivity and potency.

Structural characterization of a lepidopteran type-II farnesyl diphosphate synthase from the spruce budworm, Choristoneura fumiferana: Implications for inhibitor design.,Picard ME, Nisole A, Beliveau C, Sen S, Barbar A, Shi R, Cusson M Insect Biochem Mol Biol. 2017 Nov 25. pii: S0965-1748(17)30198-4. doi:, 10.1016/j.ibmb.2017.11.011. PMID:29183817^[1]

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

References

↑ Picard ME, Nisole A, Beliveau C, Sen S, Barbar A, Shi R, Cusson M. Structural characterization of a lepidopteran type-II farnesyl diphosphate synthase from the spruce budworm, Choristoneura fumiferana: Implications for inhibitor design. Insect Biochem Mol Biol. 2017 Nov 25. pii: S0965-1748(17)30198-4. doi:, 10.1016/j.ibmb.2017.11.011. PMID:29183817 doi:http://dx.doi.org/10.1016/j.ibmb.2017.11.011

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6b07"

Categories: Choristoneura fumiferana | Large Structures | Cusson M | Picard M-E | Shi R

@@ Line 3: / Line 3: @@
 <StructureSection load='6b07' size='340' side='right'caption='[[6b07]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b07]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Archips_fumiferana Archips fumiferana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B07 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B07 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b07]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Choristoneura_fumiferana Choristoneura fumiferana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B07 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C6M:[1-phosphono-2-(1-propylpyridin-2-yl)ethyl]phosphonic+acid'>C6M</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.98&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6b02|6b02]], [[6b04|6b04]], [[6b06|6b06]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C6M:[1-phosphono-2-(1-propylpyridin-2-yl)ethyl]phosphonic+acid'>C6M</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6b07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b07 OCA], [http://pdbe.org/6b07 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b07 RCSB], [http://www.ebi.ac.uk/pdbsum/6b07 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b07 ProSAT]</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=6b07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b07 OCA], [https://pdbe.org/6b07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b07 RCSB], [https://www.ebi.ac.uk/pdbsum/6b07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b07 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q1XAB1_CHOFU Q1XAB1_CHOFU]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Archips fumiferana]]
+[[Category: Choristoneura fumiferana]]
 [[Category: Large Structures]]
-[[Category: Cusson, M]]
+[[Category: Cusson M]]
-[[Category: Picard, M E]]
+[[Category: Picard M-E]]
-[[Category: Shi, R]]
+[[Category: Shi R]]
-[[Category: Farnesyl diphosphate synthase]]
-[[Category: Inhibitor design]]
-[[Category: Juvenile hormone]]
-[[Category: Transferase-transferase inhibitor complex]]

6b07

From Proteopedia

Revision as of 14:29, 4 October 2023

Crystal structure of CfFPPS2, a lepidopteran type-II farnesyl diphosphate synthase, complexed with [1-phosphono-2-(1-propylpyridin-2-yl)ethyl]phosphonic acid (inhibitor 1d)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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