6b07: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(2 intermediate revisions by the same user not shown)
Line 1: Line 1:


==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)==
==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)==
<StructureSection load='6b07' size='340' side='right' caption='[[6b07]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
<StructureSection load='6b07' size='340' side='right'caption='[[6b07]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
== 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>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/Q1XAB1_CHOFU Q1XAB1_CHOFU]
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>
==See Also==
 
*[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6b07" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Archips fumiferana]]
[[Category: Choristoneura fumiferana]]
[[Category: Cusson, M]]
[[Category: Large Structures]]
[[Category: Picard, M E]]
[[Category: Cusson M]]
[[Category: Shi, R]]
[[Category: Picard M-E]]
[[Category: Farnesyl diphosphate synthase]]
[[Category: Shi R]]
[[Category: Inhibitor design]]
[[Category: Juvenile hormone]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 10:29, 1 May 2024

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)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

See Also

6b07, resolution 1.98Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6b07&oldid=4138047"