4onc

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{{STRUCTURE_4onc| PDB=4onc | SCENE= }}
 
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===Crystal Structure of Mycobacterium Tuberculosis Decaprenyl Diphosphate Synthase in Complex with BPH-640===
 
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{{ABSTRACT_PUBMED_24475925}}
 
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==Function==
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==Crystal Structure of Mycobacterium Tuberculosis Decaprenyl Diphosphate Synthase in Complex with BPH-640==
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[[http://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>
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<StructureSection load='4onc' size='340' side='right'caption='[[4onc]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4onc]] is a 2 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=4ONC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ONC FirstGlance]. <br>
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</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=40B:[HYDROXY(1,1 3,1-TERPHENYL-3-YL)METHANEDIYL]BIS(PHOSPHONIC+ACID)'>40B</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4onc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4onc OCA], [https://pdbe.org/4onc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4onc RCSB], [https://www.ebi.ac.uk/pdbsum/4onc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4onc ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We have obtained the structure of the bacterial diterpene synthase, tuberculosinol/iso-tuberculosinol synthase (Rv3378c) from Mycobacterium tuberculosis , a target for anti-infective therapies that block virulence factor formation. This phosphatase adopts the same fold as found in the Z- or cis-prenyltransferases. We also obtained structures containing the tuberculosinyl diphosphate substrate together with one bisphosphonate inhibitor-bound structure. These structures together with the results of site-directed mutagenesis suggest an unusual mechanism of action involving two Tyr residues. Given the similarity in local and global structure between Rv3378c and the M. tuberculosis cis-decaprenyl diphosphate synthase (DPPS; Rv2361c), the possibility exists for the development of inhibitors that target not only virulence but also cell wall biosynthesis, based in part on the structures reported here.
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==About this Structure==
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Structure and Inhibition of Tuberculosinol Synthase and Decaprenyl Diphosphate Synthase from Mycobacterium tuberculosis.,Chan HC, Feng X, Ko TP, Huang CH, Hu Y, Zheng Y, Bogue S, Nakano C, Hoshino T, Zhang L, Lv P, Liu W, Crick DC, Liang PH, Wang AH, Oldfield E, Guo RT J Am Chem Soc. 2014 Feb 5. PMID:24475925<ref>PMID:24475925</ref>
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[[4onc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ONC OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024475925</ref><references group="xtra"/><references/>
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</div>
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[[Category: Chan, H C.]]
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<div class="pdbe-citations 4onc" style="background-color:#fffaf0;"></div>
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[[Category: Feng, X.]]
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== References ==
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[[Category: Ko, T P.]]
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<references/>
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[[Category: Decaprenyl diphosphate synthase]]
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__TOC__
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[[Category: Polyprenyl transferase]]
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</StructureSection>
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[[Category: Transferase]]
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[[Category: Large Structures]]
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[[Category: Mycobacterium tuberculosis]]
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[[Category: Chan HC]]
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[[Category: Feng X]]
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[[Category: Ko TP]]

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Crystal Structure of Mycobacterium Tuberculosis Decaprenyl Diphosphate Synthase in Complex with BPH-640

PDB ID 4onc

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