21gr: Difference between revisions

Latest revision as of 16:38, 8 September 2026

DPR epimerase complex, PMD-bound state

Structural highlights

21gr is a 4 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.73Å
Ligands:	A1L5K, FAD, NAI
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPRE2_MYCTU Component of the DprE1-DprE2 complex that catalyzes the 2-step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-phospho-arabinose (DPA), a key precursor that serves as the arabinose donor required for the synthesis of cell-wall arabinans (PubMed:16291675, PubMed:19299584). DprE1 catalyzes the first step of epimerization, namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX) (PubMed:22733761). The intermediate DPX is then transferred to DprE2 subunit of the epimerase complex, most probably through a 'substrate channel' at the interface of DprE1-DprE2 complex (PubMed:25789990). DprE2 then catalyzes the second step of epimerization, the NAD(+)-dependent reduction of DPX that leads to the formation of DPA (PubMed:22733761, PubMed:25789990). Appears to be essential for the growth and survival of M.tuberculosis (PubMed:12657046, PubMed:24517327).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

References

↑ Sassetti CM, Boyd DH, Rubin EJ. Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol. 2003 Apr;48(1):77-84. doi: 10.1046/j.1365-2958.2003.03425.x. PMID:12657046 doi:https://dx.doi.org/10.1046/j.1365-2958.2003.03425.x
↑ Mikusova K, Huang H, Yagi T, Holsters M, Vereecke D, D'Haeze W, Scherman MS, Brennan PJ, McNeil MR, Crick DC. Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose. J Bacteriol. 2005 Dec;187(23):8020-5. PMID:16291675 doi:https://dx.doi.org/10.1128/JB.187.23.8020-8025.2005
↑ Makarov V, Manina G, Mikusova K, Mollmann U, Ryabova O, Saint-Joanis B, Dhar N, Pasca MR, Buroni S, Lucarelli AP, Milano A, De Rossi E, Belanova M, Bobovska A, Dianiskova P, Kordulakova J, Sala C, Fullam E, Schneider P, McKinney JD, Brodin P, Christophe T, Waddell S, Butcher P, Albrethsen J, Rosenkrands I, Brosch R, Nandi V, Bharath S, Gaonkar S, Shandil RK, Balasubramanian V, Balganesh T, Tyagi S, Grosset J, Riccardi G, Cole ST. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science. 2009 May 8;324(5928):801-4. doi: 10.1126/science.1171583. Epub 2009 Mar , 19. PMID:19299584 doi:https://dx.doi.org/10.1126/science.1171583
↑ Batt SM, Jabeen T, Bhowruth V, Quill L, Lund PA, Eggeling L, Alderwick LJ, Futterer K, Besra GS. Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors. Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11354-9. Epub 2012 Jun 25. PMID:22733761 doi:https://dx.doi.org/10.1073/pnas.1205735109
↑ Kolly GS, Boldrin F, Sala C, Dhar N, Hartkoorn RC, Ventura M, Serafini A, McKinney JD, Manganelli R, Cole ST. Assessing the essentiality of the decaprenyl-phospho-d-arabinofuranose pathway in Mycobacterium tuberculosis using conditional mutants. Mol Microbiol. 2014 Apr;92(1):194-211. doi: 10.1111/mmi.12546. Epub 2014 Mar 7. PMID:24517327 doi:https://dx.doi.org/10.1111/mmi.12546
↑ Bhutani I, Loharch S, Gupta P, Madathil R, Parkesh R. Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies. PLoS One. 2015 Mar 19;10(3):e0119771. doi: 10.1371/journal.pone.0119771. , eCollection 2015. PMID:25789990 doi:https://dx.doi.org/10.1371/journal.pone.0119771

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Sassetti CM, Boyd DH, Rubin EJ. Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol. 2003 Apr;48(1):77-84. doi: 10.1046/j.1365-2958.2003.03425.x. PMID:12657046 doi:https://dx.doi.org/10.1046/j.1365-2958.2003.03425.x

[2] Mikusova K, Huang H, Yagi T, Holsters M, Vereecke D, D'Haeze W, Scherman MS, Brennan PJ, McNeil MR, Crick DC. Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose. J Bacteriol. 2005 Dec;187(23):8020-5. PMID:16291675 doi:https://dx.doi.org/10.1128/JB.187.23.8020-8025.2005

[3] Makarov V, Manina G, Mikusova K, Mollmann U, Ryabova O, Saint-Joanis B, Dhar N, Pasca MR, Buroni S, Lucarelli AP, Milano A, De Rossi E, Belanova M, Bobovska A, Dianiskova P, Kordulakova J, Sala C, Fullam E, Schneider P, McKinney JD, Brodin P, Christophe T, Waddell S, Butcher P, Albrethsen J, Rosenkrands I, Brosch R, Nandi V, Bharath S, Gaonkar S, Shandil RK, Balasubramanian V, Balganesh T, Tyagi S, Grosset J, Riccardi G, Cole ST. Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis. Science. 2009 May 8;324(5928):801-4. doi: 10.1126/science.1171583. Epub 2009 Mar , 19. PMID:19299584 doi:https://dx.doi.org/10.1126/science.1171583

[4] Batt SM, Jabeen T, Bhowruth V, Quill L, Lund PA, Eggeling L, Alderwick LJ, Futterer K, Besra GS. Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors. Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11354-9. Epub 2012 Jun 25. PMID:22733761 doi:https://dx.doi.org/10.1073/pnas.1205735109

[5] Kolly GS, Boldrin F, Sala C, Dhar N, Hartkoorn RC, Ventura M, Serafini A, McKinney JD, Manganelli R, Cole ST. Assessing the essentiality of the decaprenyl-phospho-d-arabinofuranose pathway in Mycobacterium tuberculosis using conditional mutants. Mol Microbiol. 2014 Apr;92(1):194-211. doi: 10.1111/mmi.12546. Epub 2014 Mar 7. PMID:24517327 doi:https://dx.doi.org/10.1111/mmi.12546

[6] Bhutani I, Loharch S, Gupta P, Madathil R, Parkesh R. Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies. PLoS One. 2015 Mar 19;10(3):e0119771. doi: 10.1371/journal.pone.0119771. , eCollection 2015. PMID:25789990 doi:https://dx.doi.org/10.1371/journal.pone.0119771

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[2]

[3]

[4]

[5]

[6]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 21gr is ON HOLD  until Paper Publication
+==DPR epimerase complex, PMD-bound state==
+<StructureSection load='21gr' size='340' side='right'caption='[[21gr]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[21gr]] is a 4 chain structure with sequence from [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=21GR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=21GR FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.73&#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=A1L5K:(6~{S})-2-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]-6-[[4-(trifluoromethyloxy)phenyl]methoxy]-6,7-dihydro-5~{H}-imidazo[2,1-b][1,3]oxazine'>A1L5K</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></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=21gr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=21gr OCA], [https://pdbe.org/21gr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=21gr RCSB], [https://www.ebi.ac.uk/pdbsum/21gr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=21gr ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DPRE2_MYCTU DPRE2_MYCTU] Component of the DprE1-DprE2 complex that catalyzes the 2-step epimerization of decaprenyl-phospho-ribose (DPR) to decaprenyl-phospho-arabinose (DPA), a key precursor that serves as the arabinose donor required for the synthesis of cell-wall arabinans (PubMed:16291675, PubMed:19299584). DprE1 catalyzes the first step of epimerization, namely FAD-dependent oxidation of the C2' hydroxyl of DPR to yield the keto intermediate decaprenyl-phospho-2'-keto-D-arabinose (DPX) (PubMed:22733761). The intermediate DPX is then transferred to DprE2 subunit of the epimerase complex, most probably through a 'substrate channel' at the interface of DprE1-DprE2 complex (PubMed:25789990). DprE2 then catalyzes the second step of epimerization, the NAD(+)-dependent reduction of DPX that leads to the formation of DPA (PubMed:22733761, PubMed:25789990). Appears to be essential for the growth and survival of M.tuberculosis (PubMed:12657046, PubMed:24517327).<ref>PMID:12657046</ref> <ref>PMID:16291675</ref> <ref>PMID:19299584</ref> <ref>PMID:22733761</ref> <ref>PMID:24517327</ref> <ref>PMID:25789990</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
+[[Category: Gao S]]
+[[Category: Rao Z]]
+[[Category: Wu F]]
+[[Category: Zhang L]]

21gr: Difference between revisions

Latest revision as of 16:38, 8 September 2026

DPR epimerase complex, PMD-bound state

Structural highlights

Function

References

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