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| | ==Structure of DocH66Y in complex with the C-terminal domain of Phd== | | ==Structure of DocH66Y in complex with the C-terminal domain of Phd== |
| - | <StructureSection load='3dd7' size='340' side='right' caption='[[3dd7]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='3dd7' size='340' side='right'caption='[[3dd7]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dd7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bpp1 Bpp1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DD7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DD7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dd7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bpp1 Bpp1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DD7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr> |
| | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dd9|3dd9]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3dd9|3dd9]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">doc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10678 BPP1])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">doc ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10678 BPP1])</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=3dd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dd7 OCA], [http://pdbe.org/3dd7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dd7 RCSB], [http://www.ebi.ac.uk/pdbsum/3dd7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dd7 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=3dd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dd7 OCA], [https://pdbe.org/3dd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dd7 RCSB], [https://www.ebi.ac.uk/pdbsum/3dd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dd7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DOC_BPP1 DOC_BPP1]] Toxic component of a toxin-antitoxin (TA) module. Overexpression results in inhibition of growth in liquid cultures and a decrease in colony formation by inhibiting translation, stabilizing mRNA and polysomes; these effects are overcome by concomitant expression of antitoxin phd. Binds 70S ribosomes and the 30S ribosomal subunits, the binding site is the same as for the antibiotic hygromycin B. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Doc and phd proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss. Overexpression of doc can induce the mRNA interferase activity of RelE in vivo.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> Antitoxin phd binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> [[http://www.uniprot.org/uniprot/PHD_BPP1 PHD_BPP1]] Antitoxin component of a toxin-antitoxin (TA) module. A labile antitoxin that binds to the doc toxin and neutralizes its toxic effect. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Phd and doc proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> Binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> | + | [[https://www.uniprot.org/uniprot/DOC_BPP1 DOC_BPP1]] Toxic component of a toxin-antitoxin (TA) module. Overexpression results in inhibition of growth in liquid cultures and a decrease in colony formation by inhibiting translation, stabilizing mRNA and polysomes; these effects are overcome by concomitant expression of antitoxin phd. Binds 70S ribosomes and the 30S ribosomal subunits, the binding site is the same as for the antibiotic hygromycin B. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Doc and phd proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss. Overexpression of doc can induce the mRNA interferase activity of RelE in vivo.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> Antitoxin phd binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> [[https://www.uniprot.org/uniprot/PHD_BPP1 PHD_BPP1]] Antitoxin component of a toxin-antitoxin (TA) module. A labile antitoxin that binds to the doc toxin and neutralizes its toxic effect. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Phd and doc proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> Binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.<ref>PMID:9829946</ref> <ref>PMID:18398006</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bpp1]] | | [[Category: Bpp1]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Garcia-Pino, A]] | | [[Category: Garcia-Pino, A]] |
| | [[Category: Loris, R]] | | [[Category: Loris, R]] |
| | [[Category: All alpha]] | | [[Category: All alpha]] |
| | [[Category: Ribosome inhibitor]] | | [[Category: Ribosome inhibitor]] |
| Structural highlights
Function
[DOC_BPP1] Toxic component of a toxin-antitoxin (TA) module. Overexpression results in inhibition of growth in liquid cultures and a decrease in colony formation by inhibiting translation, stabilizing mRNA and polysomes; these effects are overcome by concomitant expression of antitoxin phd. Binds 70S ribosomes and the 30S ribosomal subunits, the binding site is the same as for the antibiotic hygromycin B. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Doc and phd proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss. Overexpression of doc can induce the mRNA interferase activity of RelE in vivo.[1] [2] Antitoxin phd binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.[3] [4] [PHD_BPP1] Antitoxin component of a toxin-antitoxin (TA) module. A labile antitoxin that binds to the doc toxin and neutralizes its toxic effect. Bacteriophage P1 lysogenizes bacteria as a low-copy number plasmid. Phd and doc proteins function in unison to stabilize plasmid number by inducing a lethal response to P1 plasmid prophage loss.[5] [6] Binds to its own promoter repressing its expression; toxin doc acts as a corepressor or derepressor depending on the ratio, repressing or inducing expression.[7] [8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Prokaryotic toxin-antitoxin modules are involved in major physiological events set in motion under stress conditions. The toxin Doc (death on curing) from the phd/doc module on phage P1 hosts the C-terminal domain of its antitoxin partner Phd (prevents host death) through fold complementation. This Phd domain is intrinsically disordered in solution and folds into an alpha-helix upon binding to Doc. The details of the interactions reveal the molecular basis for the inhibitory action of the antitoxin. The complex resembles the Fic (filamentation induced by cAMP) proteins and suggests a possible evolutionary origin for the phd/doc operon. Doc induces growth arrest of Escherichia coli cells in a reversible manner, by targeting the protein synthesis machinery. Moreover, Doc activates the endogenous E. coli RelE mRNA interferase but does not require this or any other known chromosomal toxin-antitoxin locus for its action in vivo.
Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation.,Garcia-Pino A, Christensen-Dalsgaard M, Wyns L, Yarmolinsky M, Magnuson RD, Gerdes K, Loris R J Biol Chem. 2008 Nov 7;283(45):30821-7. Epub 2008 Aug 30. PMID:18757857[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Magnuson R, Yarmolinsky MB. Corepression of the P1 addiction operon by Phd and Doc. J Bacteriol. 1998 Dec;180(23):6342-51. PMID:9829946
- ↑ Liu M, Zhang Y, Inouye M, Woychik NA. Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit. Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5885-90. doi:, 10.1073/pnas.0711949105. Epub 2008 Apr 8. PMID:18398006 doi:10.1073/pnas.0711949105
- ↑ Magnuson R, Yarmolinsky MB. Corepression of the P1 addiction operon by Phd and Doc. J Bacteriol. 1998 Dec;180(23):6342-51. PMID:9829946
- ↑ Liu M, Zhang Y, Inouye M, Woychik NA. Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit. Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5885-90. doi:, 10.1073/pnas.0711949105. Epub 2008 Apr 8. PMID:18398006 doi:10.1073/pnas.0711949105
- ↑ Magnuson R, Yarmolinsky MB. Corepression of the P1 addiction operon by Phd and Doc. J Bacteriol. 1998 Dec;180(23):6342-51. PMID:9829946
- ↑ Liu M, Zhang Y, Inouye M, Woychik NA. Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit. Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5885-90. doi:, 10.1073/pnas.0711949105. Epub 2008 Apr 8. PMID:18398006 doi:10.1073/pnas.0711949105
- ↑ Magnuson R, Yarmolinsky MB. Corepression of the P1 addiction operon by Phd and Doc. J Bacteriol. 1998 Dec;180(23):6342-51. PMID:9829946
- ↑ Liu M, Zhang Y, Inouye M, Woychik NA. Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit. Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5885-90. doi:, 10.1073/pnas.0711949105. Epub 2008 Apr 8. PMID:18398006 doi:10.1073/pnas.0711949105
- ↑ Garcia-Pino A, Christensen-Dalsgaard M, Wyns L, Yarmolinsky M, Magnuson RD, Gerdes K, Loris R. Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation. J Biol Chem. 2008 Nov 7;283(45):30821-7. Epub 2008 Aug 30. PMID:18757857 doi:10.1074/jbc.M805654200
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