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| - | [[Image:2vg2.jpg|left|200px]]<br /><applet load="2vg2" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2vg2, resolution 1.95Å" /> | |
| - | '''RV2361 WITH IPP'''<br /> | |
| | | | |
| - | ==About this Structure== | + | ==Rv2361 with IPP== |
| - | 2VG2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=PO4:'>PO4</scene>, <scene name='pdbligand=DPO:'>DPO</scene>, <scene name='pdbligand=IPE:'>IPE</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Di-trans,poly-cis-decaprenylcistransferase Di-trans,poly-cis-decaprenylcistransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.31 2.5.1.31] Known structural/functional Sites: <scene name='pdbsite=AC1:Dpo+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Dpo+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Dpo+Binding+Site+For+Chain+C'>AC3</scene>, <scene name='pdbsite=AC4:Po4+Binding+Site+For+Chain+C'>AC4</scene>, <scene name='pdbsite=AC5:Po4+Binding+Site+For+Chain+D'>AC5</scene>, <scene name='pdbsite=AC6:Ipe+Binding+Site+For+Chain+A'>AC6</scene>, <scene name='pdbsite=AC7:Ipe+Binding+Site+For+Chain+B'>AC7</scene>, <scene name='pdbsite=AC8:Gol+Binding+Site+For+Chain+B'>AC8</scene>, <scene name='pdbsite=AC9:Gol+Binding+Site+For+Chain+A'>AC9</scene>, <scene name='pdbsite=BC1:Gol+Binding+Site+For+Chain+A'>BC1</scene>, <scene name='pdbsite=BC2:Gol+Binding+Site+For+Chain+B'>BC2</scene>, <scene name='pdbsite=BC3:Gol+Binding+Site+For+Chain+B'>BC3</scene>, <scene name='pdbsite=BC4:Gol+Binding+Site+For+Chain+C'>BC4</scene>, <scene name='pdbsite=BC5:Gol+Binding+Site+For+Chain+C'>BC5</scene>, <scene name='pdbsite=BC6:Gol+Binding+Site+For+Chain+C'>BC6</scene>, <scene name='pdbsite=BC7:Gol+Binding+Site+For+Chain+B'>BC7</scene>, <scene name='pdbsite=BC8:Gol+Binding+Site+For+Chain+A'>BC8</scene>, <scene name='pdbsite=BC9:Gol+Binding+Site+For+Chain+A'>BC9</scene>, <scene name='pdbsite=CC1:Gol+Binding+Site+For+Chain+A'>CC1</scene>, <scene name='pdbsite=CC2:Cl+Binding+Site+For+Chain+A'>CC2</scene>, <scene name='pdbsite=CC3:Po4+Binding+Site+For+Chain+C'>CC3</scene>, <scene name='pdbsite=CC4:Po4+Binding+Site+For+Chain+A'>CC4</scene> and <scene name='pdbsite=CC5:Po4+Binding+Site+For+Chain+D'>CC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VG2 OCA].
| + | <StructureSection load='2vg2' size='340' side='right'caption='[[2vg2]], [[Resolution|resolution]] 1.95Å' scene=''> |
| - | [[Category: Di-trans,poly-cis-decaprenylcistransferase]] | + | == Structural highlights == |
| - | [[Category: Mycobacterium tuberculosis]] | + | <table><tr><td colspan='2'>[[2vg2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VG2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VG2 FirstGlance]. <br> |
| - | [[Category: Single protein]]
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> |
| - | [[Category: Dong, C.]]
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DPO:DIPHOSPHATE'>DPO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | [[Category: Naismith, J H.]] | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vg2 OCA], [https://pdbe.org/2vg2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vg2 RCSB], [https://www.ebi.ac.uk/pdbsum/2vg2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vg2 ProSAT]</span></td></tr> |
| - | [[Category: Wang, W.]]
| + | </table> |
| - | [[Category: CL]]
| + | == Function == |
| - | [[Category: DPO]]
| + | [https://www.uniprot.org/uniprot/DPDS_MYCTU DPDS_MYCTU] Catalyzes the sequential condensation of isopentenyl diphosphate (IPP) in the cis configuration with (2Z,6E)-farnesyl diphosphate (Z-FPP or EZ-FPP) generating the 50 carbon product trans,polycis-decaprenyl diphosphate. When (2E,6E)-farnesyl diphosphate (E-FPP or EE-FPP) is used in vitro, both primary products decaprenyl diphosphate and (2E,6E,10E)-geranylgeranyl diphosphate (EEE-GGPP) are synthesized. M.tuberculosis does not synthesize (2E,6E,10Z)-geranylgeranyl diphosphate (EEZ-GGPP) and heptaprenyl diphosphate. Can also accept many different allylic substrates, including E-geranyl diphosphate (E-GPP), neryl diphosphate (NPP), and all-trans-geranyl-geranyl diphosphate.<ref>PMID:11004176</ref> <ref>PMID:10816587</ref> <ref>PMID:15516568</ref> |
| - | [[Category: GOL]] | + | == Evolutionary Conservation == |
| - | [[Category: IPE]] | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | [[Category: PO4]] | + | Check<jmol> |
| - | [[Category: cell cycle]] | + | <jmolCheckbox> |
| - | [[Category: cell division]]
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vg/2vg2_consurf.spt"</scriptWhenChecked> |
| - | [[Category: cell shape]]
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | [[Category: cell wall biogenesis/degradation]]
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | [[Category: peptidoglycan synthesis]]
| + | </jmolCheckbox> |
| - | [[Category: prenyl transferase]]
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vg2 ConSurf]. |
| - | [[Category: transferase]]
| + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | In Mycobacterium tuberculosis, two related Z-prenyl diphosphate synthases, E,Z-farnesyl diphosphate synthase (Rv1086) and decaprenyl diphosphate synthase (Rv2361c), work in series to synthesize decaprenyl phosphate (C(50)) from isopentenyl diphosphate and E-geranyl diphosphate. Decaprenyl phosphate plays a central role in the biosynthesis of essential mycobacterial cell wall components, such as the mycolyl-arabinogalactan-peptidoglycan complex and lipoarabinomannan; thus, its synthesis has attracted considerable interest as a potential therapeutic target. Rv1086 is a unique prenyl diphosphate synthase in that it adds only one isoprene unit to geranyl diphosphate, generating the 15-carbon product (E,Z-farnesyl diphosphate). Rv2361c then adds a further seven isoprene units to E,Z-farnesyl diphosphate in a processive manner to generate the 50-carbon prenyl diphosphate, which is then dephosphorylated to generate a carrier for activated sugars. The molecular basis for chain-length discrimination by Rv1086 during synthesis is unknown. We also report the structure of apo Rv1086 with citronellyl diphosphate bound and with the product mimic E,E-farnesyl diphosphate bound. We report the structures of Rv2361c in the apo form, with isopentenyl diphosphate bound and with a substrate analogue, citronellyl diphosphate. The structures confirm the enzymes are very closely related. Detailed comparison reveals structural differences that account for chain-length control in Rv1086. We have tested this hypothesis and have identified a double mutant of Rv1086 that makes a range of longer lipid chains. |
| | | | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:55:34 2008''
| + | The structural basis of chain length control in Rv1086.,Wang W, Dong C, McNeil M, Kaur D, Mahapatra S, Crick DC, Naismith JH J Mol Biol. 2008 Aug 1;381(1):129-40. Epub 2008 Jul 1. PMID:18597781<ref>PMID:18597781</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2vg2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Undecaprenyl pyrophosphate synthase 3D structures|Undecaprenyl pyrophosphate synthase 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | + | [[Category: Mycobacterium tuberculosis]] |
| | + | [[Category: Dong C]] |
| | + | [[Category: Naismith JH]] |
| | + | [[Category: Wang W]] |
| Structural highlights
2vg2 is a 4 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.95Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
DPDS_MYCTU Catalyzes the sequential condensation of isopentenyl diphosphate (IPP) in the cis configuration with (2Z,6E)-farnesyl diphosphate (Z-FPP or EZ-FPP) generating the 50 carbon product trans,polycis-decaprenyl diphosphate. When (2E,6E)-farnesyl diphosphate (E-FPP or EE-FPP) is used in vitro, both primary products decaprenyl diphosphate and (2E,6E,10E)-geranylgeranyl diphosphate (EEE-GGPP) are synthesized. M.tuberculosis does not synthesize (2E,6E,10Z)-geranylgeranyl diphosphate (EEZ-GGPP) and heptaprenyl diphosphate. Can also accept many different allylic substrates, including E-geranyl diphosphate (E-GPP), neryl diphosphate (NPP), and all-trans-geranyl-geranyl diphosphate.[1] [2] [3]
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
In Mycobacterium tuberculosis, two related Z-prenyl diphosphate synthases, E,Z-farnesyl diphosphate synthase (Rv1086) and decaprenyl diphosphate synthase (Rv2361c), work in series to synthesize decaprenyl phosphate (C(50)) from isopentenyl diphosphate and E-geranyl diphosphate. Decaprenyl phosphate plays a central role in the biosynthesis of essential mycobacterial cell wall components, such as the mycolyl-arabinogalactan-peptidoglycan complex and lipoarabinomannan; thus, its synthesis has attracted considerable interest as a potential therapeutic target. Rv1086 is a unique prenyl diphosphate synthase in that it adds only one isoprene unit to geranyl diphosphate, generating the 15-carbon product (E,Z-farnesyl diphosphate). Rv2361c then adds a further seven isoprene units to E,Z-farnesyl diphosphate in a processive manner to generate the 50-carbon prenyl diphosphate, which is then dephosphorylated to generate a carrier for activated sugars. The molecular basis for chain-length discrimination by Rv1086 during synthesis is unknown. We also report the structure of apo Rv1086 with citronellyl diphosphate bound and with the product mimic E,E-farnesyl diphosphate bound. We report the structures of Rv2361c in the apo form, with isopentenyl diphosphate bound and with a substrate analogue, citronellyl diphosphate. The structures confirm the enzymes are very closely related. Detailed comparison reveals structural differences that account for chain-length control in Rv1086. We have tested this hypothesis and have identified a double mutant of Rv1086 that makes a range of longer lipid chains.
The structural basis of chain length control in Rv1086.,Wang W, Dong C, McNeil M, Kaur D, Mahapatra S, Crick DC, Naismith JH J Mol Biol. 2008 Aug 1;381(1):129-40. Epub 2008 Jul 1. PMID:18597781[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Crick DC, Schulbach MC, Zink EE, Macchia M, Barontini S, Besra GS, Brennan PJ. Polyprenyl phosphate biosynthesis in Mycobacterium tuberculosis and Mycobacterium smegmatis. J Bacteriol. 2000 Oct;182(20):5771-8. PMID:11004176
- ↑ Schulbach MC, Brennan PJ, Crick DC. Identification of a short (C15) chain Z-isoprenyl diphosphate synthase and a homologous long (C50) chain isoprenyl diphosphate synthase in Mycobacterium tuberculosis. J Biol Chem. 2000 Jul 28;275(30):22876-81. PMID:10816587 doi:http://dx.doi.org/10.1074/jbc.M003194200
- ↑ Kaur D, Brennan PJ, Crick DC. Decaprenyl diphosphate synthesis in Mycobacterium tuberculosis. J Bacteriol. 2004 Nov;186(22):7564-70. PMID:15516568 doi:http://dx.doi.org/10.1128/JB.186.22.7564-7570.2004
- ↑ Wang W, Dong C, McNeil M, Kaur D, Mahapatra S, Crick DC, Naismith JH. The structural basis of chain length control in Rv1086. J Mol Biol. 2008 Aug 1;381(1):129-40. Epub 2008 Jul 1. PMID:18597781 doi:10.1016/j.jmb.2008.05.060
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