PDBsum entry 3i54

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protein ligands Protein-protein interface(s) links
DNA binding protein PDB id
Protein chains
224 a.a. *
206 a.a. *
CMP ×4
Waters ×102
* Residue conservation analysis
PDB id:
Name: DNA binding protein
Title: Crystal structure of mtbcrp in complex with camp
Structure: Transcriptional regulator, crp/fnr family. Chain: a, b, c, d. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: mt3777, rv3676. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.20Å     R-factor:   0.213     R-free:   0.266
Authors: M.C.Reddy,S.K.Palaninathan,J.B.Bruning,C.Thurman,D.Smith, J.C.Sacchettini,Tb Structural Genomics Consortium (Tbsgc)
Key ref: M.C.Reddy et al. (2009). Structural insights into the mechanism of the allosteric transitions of Mycobacterium tuberculosis cAMP receptor protein. J Biol Chem, 284, 36581-36591. PubMed id: 19740754
03-Jul-09     Release date:   08-Sep-09    
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Protein chains
P9WMH3  (CRP_MYCTU) -  cAMP receptor protein
224 a.a.
224 a.a.
Protein chain
P9WMH3  (CRP_MYCTU) -  cAMP receptor protein
224 a.a.
206 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   3 terms 
  Biological process     growth   6 terms 
  Biochemical function     nucleotide binding     5 terms  


J Biol Chem 284:36581-36591 (2009)
PubMed id: 19740754  
Structural insights into the mechanism of the allosteric transitions of Mycobacterium tuberculosis cAMP receptor protein.
M.C.Reddy, S.K.Palaninathan, J.B.Bruning, C.Thurman, D.Smith, J.C.Sacchettini.
The cAMP receptor protein (CRP) from Mycobacterium tuberculosis is a cAMP-responsive global transcriptional regulator, responsible for the regulation of a multitude of diverse proteins. We have determined the crystal structures of the CRP.cAMP and CRP.N(6)-cAMP derivative-bound forms of the enzyme to 2.2- and 2.3 A-resolution, respectively, to investigate cAMP-mediated conformational and structural changes. The allosteric switch from the open, inactive conformation to the closed, active conformation begins with a number of changes in the ligand-binding cavity upon cAMP binding. These subtle structural changes and numerous non-bonding interactions between cAMP, the N-domain residues, and the C-domain helices demonstrate that the N-domain hairpin loop acts as a structural mediator of the allosteric switch. Based on the CRP.N(6)-cAMP crystal structure, binding of N(6)-cAMP with a bulkier methylphenylethyl extension from the N6 atom stabilizes the cAMP-binding domain, N-domain hairpin, and C-terminal domain in a similar manner as that of the CRP.cAMP structure, maintaining structural integrity within the subunits. However, the bulkier N6 extension of N(6)-cAMP (in R conformation) is accommodated only in subunit A with minor changes, whereas in subunit B, the N6 extension is in the S conformation hindering the hinge region of the central helix. As a result, the entire N-domain and the C-domain of subunit B integrated by the cAMP portion of this ligand, together tilt away ( approximately 7 degrees tilt) from central helix C, positioning the helix-turn-helix motif in an unfavorable position for the DNA substrate, asymmetrically. Together, these crystal structures demonstrate the mechanism of action of the cAMP molecule and its role in integrating the active CRP structure.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21199259 G.Bai, G.S.Knapp, and K.A.McDonough (2011).
Cyclic AMP signalling in mycobacteria: redirecting the conversation with a common currency.
  Cell Microbiol, 13, 349-358.  
20028978 M.Stapleton, I.Haq, D.M.Hunt, K.B.Arnvig, P.J.Artymiuk, R.S.Buxton, and J.Green (2010).
Mycobacterium tuberculosis cAMP receptor protein (Rv3676) differs from the Escherichia coli paradigm in its cAMP binding and DNA binding properties and transcription activation properties.
  J Biol Chem, 285, 7016-7027.  
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