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| | ==Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose-6-phosphate and fructose-1,6-bisphosphate== | | ==Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose-6-phosphate and fructose-1,6-bisphosphate== |
| - | <StructureSection load='2oen' size='340' side='right' caption='[[2oen]], [[Resolution|resolution]] 3.17Å' scene=''> | + | <StructureSection load='2oen' size='340' side='right'caption='[[2oen]], [[Resolution|resolution]] 3.17Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2oen]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14581 Atcc 14581]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OEN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2oen]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_14581 Atcc 14581]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OEN FirstGlance]. <br> |
| | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2nzu|2nzu]], [[2nzv|2nzv]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2nzu|2nzu]], [[2nzv|2nzv]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ccpA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1404 ATCC 14581]), ptsH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1404 ATCC 14581])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ccpA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1404 ATCC 14581]), ptsH ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1404 ATCC 14581])</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=2oen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oen OCA], [http://pdbe.org/2oen PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2oen RCSB], [http://www.ebi.ac.uk/pdbsum/2oen PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2oen 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=2oen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oen OCA], [https://pdbe.org/2oen PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oen RCSB], [https://www.ebi.ac.uk/pdbsum/2oen PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oen ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CCPA_BACME CCPA_BACME]] Global transcriptional regulator of carbon catabolite repression (CCR) and carbon catabolite activation (CCA), which ensures optimal energy usage under diverse conditions (By similarity). [[http://www.uniprot.org/uniprot/PTHP_BACME PTHP_BACME]] General (non sugar-specific) component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS). This major carbohydrate active-transport system catalyzes the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane. The phosphoryl group from phosphoenolpyruvate (PEP) is transferred to the phosphoryl carrier protein HPr by enzyme I. Phospho-HPr then transfers it to the permease (enzymes II/III) (By similarity). P-Ser-HPr interacts with the catabolite control protein A (CcpA), forming a complex that binds to DNA at the catabolite response elements cre, operator sites preceding a large number of catabolite-regulated genes. Thus, P-Ser-HPr is a corepressor in carbon catabolite repression (CCR), a mechanism that allows bacteria to coordinate and optimize the utilization of available carbon sources. P-Ser-HPr also plays a role in inducer exclusion, in which it probably interacts with several non-PTS permeases and inhibits their transport activity (By similarity). | + | [[https://www.uniprot.org/uniprot/CCPA_BACME CCPA_BACME]] Global transcriptional regulator of carbon catabolite repression (CCR) and carbon catabolite activation (CCA), which ensures optimal energy usage under diverse conditions (By similarity). [[https://www.uniprot.org/uniprot/PTHP_BACME PTHP_BACME]] General (non sugar-specific) component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS). This major carbohydrate active-transport system catalyzes the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane. The phosphoryl group from phosphoenolpyruvate (PEP) is transferred to the phosphoryl carrier protein HPr by enzyme I. Phospho-HPr then transfers it to the permease (enzymes II/III) (By similarity). P-Ser-HPr interacts with the catabolite control protein A (CcpA), forming a complex that binds to DNA at the catabolite response elements cre, operator sites preceding a large number of catabolite-regulated genes. Thus, P-Ser-HPr is a corepressor in carbon catabolite repression (CCR), a mechanism that allows bacteria to coordinate and optimize the utilization of available carbon sources. P-Ser-HPr also plays a role in inducer exclusion, in which it probably interacts with several non-PTS permeases and inhibits their transport activity (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Catabolite control protein|Catabolite control protein]] | + | *[[Catabolite control protein 3D structures|Catabolite control protein 3D structures]] |
| - | *[[Phosphocarrier protein|Phosphocarrier protein]] | + | *[[Phosphocarrier protein HPr 3D structures|Phosphocarrier protein HPr 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Atcc 14581]] | | [[Category: Atcc 14581]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Brennan, R G]] | | [[Category: Brennan, R G]] |
| | [[Category: Hillen, W]] | | [[Category: Hillen, W]] |
| Structural highlights
Function
[CCPA_BACME] Global transcriptional regulator of carbon catabolite repression (CCR) and carbon catabolite activation (CCA), which ensures optimal energy usage under diverse conditions (By similarity). [PTHP_BACME] General (non sugar-specific) component of the phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS). This major carbohydrate active-transport system catalyzes the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane. The phosphoryl group from phosphoenolpyruvate (PEP) is transferred to the phosphoryl carrier protein HPr by enzyme I. Phospho-HPr then transfers it to the permease (enzymes II/III) (By similarity). P-Ser-HPr interacts with the catabolite control protein A (CcpA), forming a complex that binds to DNA at the catabolite response elements cre, operator sites preceding a large number of catabolite-regulated genes. Thus, P-Ser-HPr is a corepressor in carbon catabolite repression (CCR), a mechanism that allows bacteria to coordinate and optimize the utilization of available carbon sources. P-Ser-HPr also plays a role in inducer exclusion, in which it probably interacts with several non-PTS permeases and inhibits their transport activity (By similarity).
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
In Gram-positive bacteria, carbon catabolite regulation (CCR) is mediated by the carbon catabolite control protein A (CcpA), a member of the LacI-GalR family of transcription regulators. Unlike other LacI-GalR proteins, CcpA is activated to bind DNA by binding the phosphoproteins HPr-Ser46-P or Crh-Ser46-P. However, fine regulation of CCR is accomplished by the small molecule effectors, glucose 6-phosphate (G6P) and fructose 1,6-bisphosphate (FBP), which somehow enhance CcpA-(HPr-Ser46-P) binding to DNA. Unlike the CcpA-(HPr-Ser46-P) complex, DNA binding by CcpA-(Crh-Ser46-P) is not stimulated by G6P or FBP. To understand the fine-tuning mechanism of these effectors, we solved the structures of the CcpA core, DeltaCcpA, which lacks the N-terminal DNA-binding domain, in complex with HPr-Ser46-P and G6P or FBP. G6P and FBP bind in a deep cleft, between the N and C subdomains of CcpA. Neither interacts with HPr-Ser46-P. This suggests that one role of the adjunct corepressors is to buttress the DNA-binding conformation effected by the binding of HPr-Ser46-P to the CcpA dimer N subdomains. However, the structures reveal that an unexpected function of adjunct corepressor binding is to bolster cross interactions between HPr-Ser46-P residue Arg17 and residues Asp69 and Asp99 of the other CcpA subunit. These cross contacts, which are weak or not present in the CcpA-(Crh-Ser46-P) complex, stimulate the CcpA-(HPr-Ser46-P)-DNA interaction specifically. Thus, stabilization of the closed conformation and bolstering of cross contacts between CcpA and its other corepressor, HPr-Ser46-P, provide a molecular explanation for how adjunct corepressors G6P and FBP enhance the interaction between CcpA-(HPr-Ser46-P) and cognate DNA.
Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose 6-phosphate and fructose 1,6-bisphosphate.,Schumacher MA, Seidel G, Hillen W, Brennan RG J Mol Biol. 2007 May 11;368(4):1042-50. Epub 2007 Feb 27. PMID:17376479[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schumacher MA, Seidel G, Hillen W, Brennan RG. Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose 6-phosphate and fructose 1,6-bisphosphate. J Mol Biol. 2007 May 11;368(4):1042-50. Epub 2007 Feb 27. PMID:17376479 doi:10.1016/j.jmb.2007.02.054
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