This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6b04

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 14:29, 4 October 2023

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

Structural highlights

6b04 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 1.83Å
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/6b04"

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

@@ Line 3: / Line 3: @@
 <StructureSection load='6b04' size='340' side='right'caption='[[6b04]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b04]] 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=6B04 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B04 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b04]] 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=6B04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B04 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C6J:[2-(1-methylpyridin-2-yl)-1-phosphono-ethyl]phosphonic+acid'>C6J</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]] 1.83&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6b02|6b02]], [[6b06|6b06]], [[6b07|6b07]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C6J:[2-(1-methylpyridin-2-yl)-1-phosphono-ethyl]phosphonic+acid'>C6J</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=6b04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b04 OCA], [http://pdbe.org/6b04 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b04 RCSB], [http://www.ebi.ac.uk/pdbsum/6b04 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b04 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=6b04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b04 OCA], [https://pdbe.org/6b04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b04 RCSB], [https://www.ebi.ac.uk/pdbsum/6b04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b04 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]]

6b04

From Proteopedia

Revision as of 14:29, 4 October 2023

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox