4qvh

From Proteopedia

(Difference between revisions)

Revision as of 13:54, 22 February 2023

Crystal structure of the essential Mycobacterium tuberculosis phosphopantetheinyl transferase PptT, solved as a fusion protein with maltose binding protein

Structural highlights

4qvh is a 2 chain structure with sequence from Escherichia coli and Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.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]

Publication Abstract from PubMed

Phosphopantetheinyl transferases (PPTases) are key enzymes in the assembly-line production of complex molecules such as fatty acids, polyketides and polypeptides, where they activate acyl or peptidyl carrier proteins, transferring a 4'-phosphopantetheinyl moiety from coenzyme A (CoA) to a reactive serine residue on the carrier protein. The human pathogen Mycobacterium tuberculosis encodes two PPTases, both essential and therefore attractive drug targets. We report the structure of the type-II PPTase PptT, obtained from crystals of a fusion protein with maltose binding protein. The structure, at 1.75A resolution (R=0.156, Rfree=0.191), reveals an alpha/beta fold broadly similar to other type-II PPTases, but with differences in peripheral structural elements. A bound CoA is clearly defined with its pantetheinyl arm tucked into a hydrophobic pocket. Interactions involving the CoA diphosphate, bound Mg2+ and three active site acidic side chains suggest a plausible pathway for proton transfer during catalysis.

Crystal structure of the essential Mycobacterium tuberculosis phosphopantetheinyl transferase PptT, solved as a fusion protein with maltose binding protein.,Jung J, Bashiri G, Johnston JM, Brown AS, Ackerley DF, Baker EN J Struct Biol. 2014 Oct 18;188(3):274-278. doi: 10.1016/j.jsb.2014.10.004. PMID:25450595^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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:http://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:http://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:http://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:http://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:http://dx.doi.org/10.1371/journal.ppat.1003097
↑ Jung J, Bashiri G, Johnston JM, Brown AS, Ackerley DF, Baker EN. Crystal structure of the essential Mycobacterium tuberculosis phosphopantetheinyl transferase PptT, solved as a fusion protein with maltose binding protein. J Struct Biol. 2014 Oct 18;188(3):274-278. doi: 10.1016/j.jsb.2014.10.004. PMID:25450595 doi:http://dx.doi.org/10.1016/j.jsb.2014.10.004

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qvh"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the essential Mycobacterium tuberculosis phosphopantetheinyl transferase PptT, solved as a fusion protein with maltose binding protein==
-<StructureSection load='4qvh' size='340' side='right' caption='[[4qvh]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+<StructureSection load='4qvh' size='340' side='right'caption='[[4qvh]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4qvh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QVH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QVH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4qvh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QVH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">malE, pptT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=4qvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qvh OCA], [https://pdbe.org/4qvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qvh RCSB], [https://www.ebi.ac.uk/pdbsum/4qvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qvh ProSAT]</span></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=4qvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qvh OCA], [http://pdbe.org/4qvh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qvh RCSB], [http://www.ebi.ac.uk/pdbsum/4qvh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qvh ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.
+[https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Myctu]]
+[[Category: Escherichia coli]]
-[[Category: Baker, E N]]
+[[Category: Large Structures]]
-[[Category: Bashiri, G]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Johnston, J M]]
+[[Category: Baker EN]]
-[[Category: Jung, J]]
+[[Category: Bashiri G]]
-[[Category: A/b-fold]]
+[[Category: Johnston JM]]
-[[Category: Acyl carrier protein]]
+[[Category: Jung J]]
-[[Category: Peptidyl carrier protein]]
-[[Category: Phosphopantetheinyl transferase]]
-[[Category: Transferase]]

4qvh

From Proteopedia

Revision as of 13:54, 22 February 2023

Crystal structure of the essential Mycobacterium tuberculosis phosphopantetheinyl transferase PptT, solved as a fusion protein with maltose binding protein

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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