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6uw7

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Current revision (07:59, 11 October 2023) (edit) (undo)
 
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<StructureSection load='6uw7' size='340' side='right'caption='[[6uw7]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
<StructureSection load='6uw7' size='340' side='right'caption='[[6uw7]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6uw7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UW7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UW7 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6uw7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UW7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UW7 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QMD:2-[oxidanyl-[(2~{R},3~{S},4~{S})-2,3,4-tris(oxidanyl)-5-[2,4,8-tris(oxidanylidene)-1,9-dihydropyrimido[4,5-b]quinolin-10-yl]pentoxy]phosphoryl]oxyprop-2-enoic+acid'>QMD</scene></td></tr>
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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]] 2.342&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6uvx|6uvx]], [[6uw1|6uw1]], [[6uw3|6uw3]], [[6uw5|6uw5]]</div></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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QMD:2-[oxidanyl-[(2~{R},3~{S},4~{S})-2,3,4-tris(oxidanyl)-5-[2,4,8-tris(oxidanylidene)-1,9-dihydropyrimido[4,5-b]quinolin-10-yl]pentoxy]phosphoryl]oxyprop-2-enoic+acid'>QMD</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fbiA, MSMEG_1830, MSMEI_1787 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphoenolpyruvate_transferase Phosphoenolpyruvate transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.8.28 2.7.8.28] </span></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=6uw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uw7 OCA], [https://pdbe.org/6uw7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uw7 RCSB], [https://www.ebi.ac.uk/pdbsum/6uw7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uw7 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=6uw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uw7 OCA], [https://pdbe.org/6uw7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uw7 RCSB], [https://www.ebi.ac.uk/pdbsum/6uw7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uw7 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/FBIA_MYCS2 FBIA_MYCS2]] Catalyzes the transfer of the phosphoenolpyruvate moiety from enoylpyruvoyl-2-diphospho-5'-guanosine (EPPG) to 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) with the formation of dehydro coenzyme F420-0 and GMP.
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[https://www.uniprot.org/uniprot/FBIA_MYCS2 FBIA_MYCS2] Catalyzes the transfer of the phosphoenolpyruvate moiety from enoylpyruvoyl-2-diphospho-5'-guanosine (EPPG) to 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) with the formation of dehydro coenzyme F420-0 and GMP.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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F420 is a low-potential redox cofactor used by diverse bacteria and archaea. In mycobacteria, this cofactor has multiple roles, including adaptation to redox stress, cell wall biosynthesis, and activation of the clinical antitubercular prodrugs pretomanid and delamanid. A recent biochemical study proposed a revised biosynthesis pathway for F420 in mycobacteria; it was suggested that phosphoenolpyruvate served as a metabolic precursor for this pathway, rather than 2-phospholactate as long proposed, but these findings were subsequently challenged. In this work, we combined metabolomic, genetic, and structural analyses to resolve these discrepancies and determine the basis of F420 biosynthesis in mycobacterial cells. We show that, in whole cells of Mycobacterium smegmatis, phosphoenolpyruvate rather than 2-phospholactate stimulates F420 biosynthesis. Analysis of F420 biosynthesis intermediates present in M. smegmatis cells harboring genetic deletions at each step of the biosynthetic pathway confirmed that phosphoenolpyruvate is then used to produce the novel precursor compound dehydro-F420-0. To determine the structural basis of dehydro-F420-0 production, we solved high-resolution crystal structures of the enzyme responsible (FbiA) in apo-, substrate-, and product-bound forms. These data show the essential role of a single divalent cation in coordinating the catalytic precomplex of this enzyme and demonstrate that dehydro-F420-0 synthesis occurs through a direct substrate transfer mechanism. Together, these findings resolve the biosynthetic pathway of F420 in mycobacteria and have significant implications for understanding the emergence of antitubercular prodrug resistance.IMPORTANCE Mycobacteria are major environmental microorganisms and cause many significant diseases, including tuberculosis. Mycobacteria make an unusual vitamin-like compound, F420, and use it to both persist during stress and resist antibiotic treatment. Understanding how mycobacteria make F420 is important, as this process can be targeted to create new drugs to combat infections like tuberculosis. In this study, we show that mycobacteria make F420 in a way that is different from other bacteria. We studied the molecular machinery that mycobacteria use to make F420, determining the chemical mechanism for this process and identifying a novel chemical intermediate. These findings also have clinical relevance, given that two new prodrugs for tuberculosis treatment are activated by F420.
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Cellular and Structural Basis of Synthesis of the Unique Intermediate Dehydro-F420-0 in Mycobacteria.,Grinter R, Ney B, Brammananth R, Barlow CK, Cordero PRF, Gillett DL, Izore T, Cryle MJ, Harold LK, Cook GM, Taiaroa G, Williamson DA, Warden AC, Oakeshott JG, Taylor MC, Crellin PK, Jackson CJ, Schittenhelm RB, Coppel RL, Greening C mSystems. 2020 May 19;5(3). pii: 5/3/e00389-20. doi: 10.1128/mSystems.00389-20. PMID:32430409<ref>PMID:32430409</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6uw7" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Mycs2]]
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[[Category: Mycolicibacterium smegmatis MC2 155]]
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[[Category: Phosphoenolpyruvate transferase]]
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[[Category: Cordero PRF]]
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[[Category: Cordero, P R.F]]
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[[Category: Gillett D]]
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[[Category: Gillett, D]]
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[[Category: Greening C]]
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[[Category: Greening, C]]
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[[Category: Grinter R]]
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[[Category: Grinter, R]]
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[[Category: Izore T]]
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[[Category: Izore, T]]
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[[Category: Biosynthetic protein]]
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[[Category: Factor 420]]
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[[Category: Metalloenzyme]]
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[[Category: Phosphotransferase]]
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Current revision

The crystal structure of FbiA from Mycobacterium smegmatis, Dehydro-F420-0 bound form

PDB ID 6uw7

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