8gkf: Difference between revisions

Latest revision as of 08:17, 20 March 2024

Phosphopantetheinyl transferase PptT from Mycobacterium tuberculosis in complex with Raltitrexed.

Structural highlights

8gkf is a 9 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 2.45Å
Ligands:	D16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PPTT_MYCTU Transfers the 4'-phosphopantetheine moiety from coenzyme A to a Ser of acyl-carrier-protein (PubMed:9831524, PubMed:16709676, PubMed:25785780, PubMed:28203522). Involved in post-translational modification of various type-I polyketide synthases required for the formation of both mycolic acids and lipid virulence factors (PubMed:16709676). Acts on Pks13, Mas, PpsA, PpsB, PpsC and PpsD (PubMed:16709676, PubMed:28203522). Also acts on AcpM, the meromycolate extension acyl carrier protein (PubMed:25785780). In addition, is involved in the activation of the acyl carrier protein MbtL and the nonribosomal peptides synthases MbtB and MbtE, which are involved in the biosynthesis of the siderophore mycobactin (PubMed:9831524, PubMed:28203522).^[1] ^[2] ^[3] ^[4] Required for the replication and survival of Mycobacterium during the acute and chronic phases of infection in mice.^[5]

References

↑ Chalut C, Botella L, de Sousa-D'Auria C, Houssin C, Guilhot C. The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8511-6. doi:, 10.1073/pnas.0511129103. Epub 2006 May 18. PMID:16709676 doi:https://dx.doi.org/10.1073/pnas.0511129103
↑ Zimhony O, Schwarz A, Raitses-Gurevich M, Peleg Y, Dym O, Albeck S, Burstein Y, Shakked Z. AcpM, the meromycolate extension acyl carrier protein of Mycobacterium tuberculosis, is activated by the 4'-phosphopantetheinyl transferase PptT, a potential target of the multistep mycolic acid biosynthesis. Biochemistry. 2015 Apr 14;54(14):2360-71. doi: 10.1021/bi501444e. Epub 2015 Apr, 1. PMID:25785780 doi:https://dx.doi.org/10.1021/bi501444e
↑ Jung J, Bashiri G, Johnston JM, Baker EN. Mass spectral determination of phosphopantetheinylation specificity for carrier proteins in Mycobacterium tuberculosis. FEBS Open Bio. 2016 Oct 24;6(12):1220-1226. doi: 10.1002/2211-5463.12140., eCollection 2016 Dec. PMID:28203522 doi:https://dx.doi.org/10.1002/2211-5463.12140
↑ Quadri LE, Sello J, Keating TA, Weinreb PH, Walsh CT. Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chem Biol. 1998 Nov;5(11):631-45. doi: 10.1016/s1074-5521(98)90291-5. PMID:9831524 doi:https://dx.doi.org/10.1016/s1074-5521(98)90291-5
↑ Leblanc C, Prudhomme T, Tabouret G, Ray A, Burbaud S, Cabantous S, Mourey L, Guilhot C, Chalut C. 4'-Phosphopantetheinyl transferase PptT, a new drug target required for Mycobacterium tuberculosis growth and persistence in vivo. PLoS Pathog. 2012 Dec;8(12):e1003097. doi: 10.1371/journal.ppat.1003097. Epub, 2012 Dec 20. PMID:23308068 doi:https://dx.doi.org/10.1371/journal.ppat.1003097

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OCA

[1] Chalut C, Botella L, de Sousa-D'Auria C, Houssin C, Guilhot C. The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8511-6. doi:, 10.1073/pnas.0511129103. Epub 2006 May 18. PMID:16709676 doi:https://dx.doi.org/10.1073/pnas.0511129103

[2] Zimhony O, Schwarz A, Raitses-Gurevich M, Peleg Y, Dym O, Albeck S, Burstein Y, Shakked Z. AcpM, the meromycolate extension acyl carrier protein of Mycobacterium tuberculosis, is activated by the 4'-phosphopantetheinyl transferase PptT, a potential target of the multistep mycolic acid biosynthesis. Biochemistry. 2015 Apr 14;54(14):2360-71. doi: 10.1021/bi501444e. Epub 2015 Apr, 1. PMID:25785780 doi:https://dx.doi.org/10.1021/bi501444e

[3] Jung J, Bashiri G, Johnston JM, Baker EN. Mass spectral determination of phosphopantetheinylation specificity for carrier proteins in Mycobacterium tuberculosis. FEBS Open Bio. 2016 Oct 24;6(12):1220-1226. doi: 10.1002/2211-5463.12140., eCollection 2016 Dec. PMID:28203522 doi:https://dx.doi.org/10.1002/2211-5463.12140

[4] Quadri LE, Sello J, Keating TA, Weinreb PH, Walsh CT. Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chem Biol. 1998 Nov;5(11):631-45. doi: 10.1016/s1074-5521(98)90291-5. PMID:9831524 doi:https://dx.doi.org/10.1016/s1074-5521(98)90291-5

[5] Leblanc C, Prudhomme T, Tabouret G, Ray A, Burbaud S, Cabantous S, Mourey L, Guilhot C, Chalut C. 4'-Phosphopantetheinyl transferase PptT, a new drug target required for Mycobacterium tuberculosis growth and persistence in vivo. PLoS Pathog. 2012 Dec;8(12):e1003097. doi: 10.1371/journal.ppat.1003097. Epub, 2012 Dec 20. PMID:23308068 doi:https://dx.doi.org/10.1371/journal.ppat.1003097

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[2]

[3]

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[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8gkf is ON HOLD  until Paper Publication
+==Phosphopantetheinyl transferase PptT from Mycobacterium tuberculosis in complex with Raltitrexed.==
+<StructureSection load='8gkf' size='340' side='right'caption='[[8gkf]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
-Authors: Krieger, I.V., Singh, A., Sacchettini, J.C., TB Structural Genomics Consortium (TBSGC)
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8gkf]] is a 9 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=8GKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GKF FirstGlance]. <br>
-Description: Phosphopantetheinyl transferase PptT from Mycobacterium tuberculosis in complex with Raltitrexed.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D16:TOMUDEX'>D16</scene></td></tr>
-[[Category: Sacchettini, J.C]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gkf OCA], [https://pdbe.org/8gkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gkf RCSB], [https://www.ebi.ac.uk/pdbsum/8gkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gkf ProSAT]</span></td></tr>
-[[Category: Krieger, I.V]]
+</table>
-[[Category: Singh, A]]
+== Function ==
-[[Category: Tb Structural Genomics Consortium (Tbsgc)]]
+[https://www.uniprot.org/uniprot/PPTT_MYCTU PPTT_MYCTU] Transfers the 4'-phosphopantetheine moiety from coenzyme A to a Ser of acyl-carrier-protein (PubMed:9831524, PubMed:16709676, PubMed:25785780, PubMed:28203522). Involved in post-translational modification of various type-I polyketide synthases required for the formation of both mycolic acids and lipid virulence factors (PubMed:16709676). Acts on Pks13, Mas, PpsA, PpsB, PpsC and PpsD (PubMed:16709676, PubMed:28203522). Also acts on AcpM, the meromycolate extension acyl carrier protein (PubMed:25785780). In addition, is involved in the activation of the acyl carrier protein MbtL and the nonribosomal peptides synthases MbtB and MbtE, which are involved in the biosynthesis of the siderophore mycobactin (PubMed:9831524, PubMed:28203522).<ref>PMID:16709676</ref> <ref>PMID:25785780</ref> <ref>PMID:28203522</ref> <ref>PMID:9831524</ref>   Required for the replication and survival of Mycobacterium during the acute and chronic phases of infection in mice.<ref>PMID:23308068</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis]]
+[[Category: Krieger IV]]
+[[Category: Sacchettini JC]]
+[[Category: Singh A]]

8gkf: Difference between revisions

Latest revision as of 08:17, 20 March 2024

Phosphopantetheinyl transferase PptT from Mycobacterium tuberculosis in complex with Raltitrexed.

Structural highlights

Function

References

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