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PDBsum entry 2wc2
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protein Protein-protein interface(s) links
Transcription regulator PDB id
2wc2

 

 

 

 

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Contents
Protein chains
209 a.a. *
* Residue conservation analysis
PDB id:
2wc2
Name: Transcription regulator
Title: Nmr structure of catabolite activator protein in the unliganded state
Structure: Catabolite gene activator. Chain: a, b. Fragment: residues 2-210. Synonym: catabolite activator protein, camp receptor protein, camp regulatory protein. Engineered: yes
Source: Escherichia coli. Organism_taxid: 469008. Expressed in: escherichia coli. Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: N.Popovych,S.R.Tzeng,C.G.Kalodimos
Key ref: N.Popovych et al. (2009). Structural basis for cAMP-mediated allosteric control of the catabolite activator protein. Proc Natl Acad Sci U S A, 106, 6927-6932. PubMed id: 19359484
Date:
06-Mar-09     Release date:   21-Apr-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0ACJ8  (CRP_ECOLI) -  DNA-binding transcriptional dual regulator CRP from Escherichia coli (strain K12)
Seq:
Struc: 		210 a.a.
209 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Proc Natl Acad Sci U S A 106:6927-6932 (2009)
PubMed id: 19359484  
 
 
Structural basis for cAMP-mediated allosteric control of the catabolite activator protein.
N.Popovych, S.R.Tzeng, M.Tonelli, R.H.Ebright, C.G.Kalodimos.
 
  ABSTRACT  
 
The cAMP-mediated allosteric transition in the catabolite activator protein (CAP; also known as the cAMP receptor protein, CRP) is a textbook example of modulation of DNA-binding activity by small-molecule binding. Here we report the structure of CAP in the absence of cAMP, which, together with structures of CAP in the presence of cAMP, defines atomic details of the cAMP-mediated allosteric transition. The structural changes, and their relationship to cAMP binding and DNA binding, are remarkably clear and simple. Binding of cAMP results in a coil-to-helix transition that extends the coiled-coil dimerization interface of CAP by 3 turns of helix and concomitantly causes rotation, by approximately 60 degrees , and translation, by approximately 7 A, of the DNA-binding domains (DBDs) of CAP, positioning the recognition helices in the DBDs in the correct orientation to interact with DNA. The allosteric transition is stabilized further by expulsion of an aromatic residue from the cAMP-binding pocket upon cAMP binding. The results define the structural mechanisms that underlie allosteric control of this prototypic transcriptional regulatory factor and provide an illustrative example of how effector-mediated structural changes can control the activity of regulatory proteins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22773105 H.J.Lee, P.T.Lang, S.M.Fortune, C.M.Sassetti, and T.Alber (2012).
Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis.
  Nat Struct Mol Biol, 19, 811-818.
PDB codes: 4ava 4avb 4avc
22801505 S.R.Tzeng, and C.G.Kalodimos (2012).
Protein activity regulation by conformational entropy.
  Nature, 488, 236-240.  
21404360 C.G.Kalodimos (2011).
NMR reveals novel mechanisms of protein activity regulation.
  Protein Sci, 20, 773-782.  
  21410646 F.J.Blanco, and G.Montoya (2011).
Transient DNA / RNA-protein interactions.
  FEBS J, 278, 1643-1650.  
21265791 G.Giardina, N.Castiglione, M.Caruso, F.Cutruzzolà, and S.Rinaldo (2011).
The Pseudomonas aeruginosa DNR transcription factor: light and shade of nitric oxide-sensing mechanisms.
  Biochem Soc Trans, 39, 294-298.  
21187420 N.L.Wicks, T.Wong, J.Sun, Z.Madden, and E.C.Young (2011).
Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating.
  Proc Natl Acad Sci U S A, 108, 609-614.  
21131971 P.Sarkar, T.Saleh, S.R.Tzeng, R.B.Birge, and C.G.Kalodimos (2011).
Structural basis for regulation of the Crk signaling protein by a proline switch.
  Nat Chem Biol, 7, 51-57.
PDB codes: 2l3p 2l3q 2l3s
21109422 S.R.Tzeng, and C.G.Kalodimos (2011).
Protein dynamics and allostery: an NMR view.
  Curr Opin Struct Biol, 21, 62-67.  
21430265 S.Schünke, M.Stoldt, J.Lecher, U.B.Kaupp, and D.Willbold (2011).
Structural insights into conformational changes of a cyclic nucleotide-binding domain in solution from Mesorhizobium loti K1 channel.
  Proc Natl Acad Sci U S A, 108, 6121-6126.
PDB code: 2kxl
20494996 E.L.Fuchs, E.D.Brutinel, A.K.Jones, N.B.Fulcher, M.L.Urbanowski, T.L.Yahr, and M.C.Wolfgang (2010).
The Pseudomonas aeruginosa Vfr regulator controls global virulence factor expression through cyclic AMP-dependent and -independent mechanisms.
  J Bacteriol, 192, 3553-3564.  
20483341 H.Toncrova, and T.C.McLeish (2010).
Substrate-modulated thermal fluctuations affect long-range allosteric signaling in protein homodimers: exemplified in CAP.
  Biophys J, 98, 2317-2326.  
21134639 J.M.Lipchock, and J.P.Loria (2010).
Nanometer propagation of millisecond motions in V-type allostery.
  Structure, 18, 1596-1607.  
20704697 M.Bhattacharyya, and S.Vishveshwara (2010).
Elucidation of the conformational free energy landscape in H.pylori LuxS and its implications to catalysis.
  BMC Struct Biol, 10, 27.  
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.  
20616047 M.X.Zhao, Y.L.Jiang, Y.X.He, Y.F.Chen, Y.B.Teng, Y.Chen, C.C.Zhang, and C.Z.Zhou (2010).
Structural basis for the allosteric control of the global transcription factor NtcA by the nitrogen starvation signal 2-oxoglutarate.
  Proc Natl Acad Sci U S A, 107, 12487-12492.
PDB codes: 3la2 3la3 3la7
20338852 P.Kumar, D.C.Joshi, M.Akif, Y.Akhter, S.E.Hasnain, and S.C.Mande (2010).
Mapping conformational transitions in cyclic AMP receptor protein: crystal structure and normal-mode analysis of Mycobacterium tuberculosis apo-cAMP receptor protein.
  Biophys J, 98, 305-314.
PDB code: 3h3u
20478828 P.Ozbek, S.Soner, B.Erman, and T.Haliloglu (2010).
DNABINDPROT: fluctuation-based predictor of DNA-binding residues within a network of interacting residues.
  Nucleic Acids Res, 38, W417-W423.  
20512974 T.J.Sjoberg, A.P.Kornev, and S.S.Taylor (2010).
Dissecting the cAMP-inducible allosteric switch in protein kinase A RIalpha.
  Protein Sci, 19, 1213-1221.
PDB code: 3iia
19822742 A.I.Arunkumar, G.C.Campanello, and D.P.Giedroc (2009).
Solution structure of a paradigm ArsR family zinc sensor in the DNA-bound state.
  Proc Natl Acad Sci U S A, 106, 18177-18182.
PDB codes: 2kjb 2kjc
19416924 B.Ma, and R.Nussinov (2009).
Amplification of signaling via cellular allosteric relay and protein disorder.
  Proc Natl Acad Sci U S A, 106, 6887-6888.  
20080782 D.Beckett (2009).
Regulating transcription regulators via allostery and flexibility.
  Proc Natl Acad Sci U S A, 106, 22035-22036.  
19805344 H.Sharma, S.Yu, J.Kong, J.Wang, and T.A.Steitz (2009).
Structure of apo-CAP reveals that large conformational changes are necessary for DNA binding.
  Proc Natl Acad Sci U S A, 106, 16604-16609.
PDB codes: 3fwe 3hif
19740754 M.C.Reddy, S.K.Palaninathan, J.B.Bruning, C.Thurman, D.Smith, and J.C.Sacchettini (2009).
Structural insights into the mechanism of the allosteric transitions of Mycobacterium tuberculosis cAMP receptor protein.
  J Biol Chem, 284, 36581-36591.
PDB codes: 3i54 3i59
19995076 N.E.Grossoehme, and D.P.Giedroc (2009).
Energetics of allosteric negative coupling in the zinc sensor S. aureus CzrA.
  J Am Chem Soc, 131, 17860-17870.  
19924217 S.R.Tzeng, and C.G.Kalodimos (2009).
Dynamic activation of an allosteric regulatory protein.
  Nature, 462, 368-372.  
19741253 Y.Luo, C.Blex, O.Baessler, M.Glinski, M.Dreger, M.Sefkow, and H.Köster (2009).
The cAMP capture compound mass spectrometry as a novel tool for targeting cAMP-binding proteins: from protein kinase A to potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channels.
  Mol Cell Proteomics, 8, 2843-2856.  
19928961 Z.Ma, D.M.Cowart, B.P.Ward, R.J.Arnold, R.D.DiMarchi, L.Zhang, G.N.George, R.A.Scott, and D.P.Giedroc (2009).
Unnatural amino acid substitution as a probe of the allosteric coupling pathway in a mycobacterial Cu(I) sensor.
  J Am Chem Soc, 131, 18044-18045.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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