Title : Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose 6-phosphate and fructose 1,6-bisphosphate.

Pub. Date : 2007 May 11

PMID : 17376479






11 Functional Relationships(s)
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1 Unlike other LacI-GalR proteins, CcpA is activated to bind DNA by binding the phosphoproteins HPr-Ser46-P or Crh-Ser46-P. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
2 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
3 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
4 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
5 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
6 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
7 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
8 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
9 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
10 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens
11 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. 2-chloro-N(6)cyclopentyladenosine haptoglobin-related protein Homo sapiens