2nzv

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(Difference between revisions)

Revision as of 23:04, 9 September 2015

Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors G6P and FBP

Structural highlights

2nzv is a 2 chain structure with sequence from Atcc 14581. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	1rzr, 1zvv, 1sxh, 1sxg, 1sxi, 2nzu
Gene:	ccpA (ATCC 14581), ptsH (ATCC 14581)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2nzv"

@@ Line 7: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rzr|1rzr]], [[1zvv|1zvv]], [[1sxh|1sxh]], [[1sxg|1sxg]], [[1sxi|1sxi]], [[2nzu|2nzu]]</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='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=2nzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nzv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2nzv RCSB], [http://www.ebi.ac.uk/pdbsum/2nzv PDBsum]</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=2nzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nzv OCA], [http://pdbe.org/2nzv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nzv RCSB], [http://www.ebi.ac.uk/pdbsum/2nzv PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2nzv" style="background-color:#fffaf0;"></div>
 ==See Also==

2nzv

From Proteopedia

Revision as of 23:04, 9 September 2015

Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors G6P and FBP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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