6b02: Difference between revisions
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==Crystal structure of CfFPPS2 (apo form), a lepidopteran type-II farnesyl diphosphate synthase== | |||
<StructureSection load='6b02' size='340' side='right' caption='[[6b02]], [[Resolution|resolution]] 2.82Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6b02]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B02 FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6b04|6b04]], [[6b06|6b06]], [[6b07|6b07]]</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=6b02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b02 OCA], [http://pdbe.org/6b02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b02 RCSB], [http://www.ebi.ac.uk/pdbsum/6b02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b02 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:29183817</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6b02" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cusson, M]] | [[Category: Cusson, M]] | ||
[[Category: Picard, M E]] | |||
[[Category: Shi, R]] | [[Category: Shi, R]] | ||
[[Category: | [[Category: Farnesyl diphosphate synthase]] | ||
[[Category: Juvenile hormone]] | |||
[[Category: Transferase]] | |||
Revision as of 10:02, 13 December 2017
Crystal structure of CfFPPS2 (apo form), a lepidopteran type-II farnesyl diphosphate synthaseCrystal structure of CfFPPS2 (apo form), a lepidopteran type-II farnesyl diphosphate synthase
Structural highlights
Publication Abstract from PubMedFarnesyl 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
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