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DNA binding protein PDB id
1g6n
Jmol
Contents
Protein chains
200 a.a. *
Ligands
CMP ×2
Waters ×115
* Residue conservation analysis
PDB id:
1g6n
Name: DNA binding protein
Title: 2.1 angstrom structure of cap-camp
Structure: Catabolite gene activator protein. Chain: a, b. Synonym: camp receptor protein. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.207    
Authors: J.M.Passner,S.C.Schultz,T.A.Steitz
Key ref: J.M.Passner et al. (2000). Modeling the cAMP-induced allosteric transition using the crystal structure of CAP-cAMP at 2.1 A resolution. J Mol Biol, 304, 847-859. PubMed id: 11124031 DOI: 10.1006/jmbi.2000.4231
Date:
07-Nov-00     Release date:   15-Dec-00    
Supersedes: 3gap
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0ACJ8  (CRP_ECOLI) -  Catabolite gene activator
Seq:
Struc: 		210 a.a.
200 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     regulation of transcription   3 terms 
  Biochemical function     nucleotide binding     7 terms  

 

 
DOI no: 10.1006/jmbi.2000.4231 J Mol Biol 304:847-859 (2000)
PubMed id: 11124031  
 
 
Modeling the cAMP-induced allosteric transition using the crystal structure of CAP-cAMP at 2.1 A resolution.
J.M.Passner, S.C.Schultz, T.A.Steitz.
 
  ABSTRACT  
 
After an allosteric transition produced by the binding of cyclic AMP (cAMP), the Escherichia coli catabolite gene activator protein (CAP) binds DNA specifically and activates transcription. The three-dimensional crystal structure of the CAP-cAMP complex has been refined at 2.1 A resolution, thus enabling a better evaluation of the structural basis for CAP phenotypes, the interactions of cAMP with CAP and the roles played by water structure. A review of mutational analysis of CAP together with the additional structural information presented here suggests a possible mechanism for the cAMP-induced allostery required for DNA binding and transcriptional activation. We hypothesize that cAMP binding may reorient the coiled-coil C-helices, which provide most of the dimer interface, thereby altering the relative positions of the DNA-binding domains of the CAP dimer. Additionally, cAMP binding may cause a further rearrangement of the DNA-binding and cAMP-binding domains of CAP via a flap consisting of beta-strands 4 and 5 which lies over the cAMP.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21404360 C.G.Kalodimos (2011).
NMR reveals novel mechanisms of protein activity regulation.
  Protein Sci, 20, 773-782.  
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.  
21214648 J.N.Marden, Q.Dong, S.Roychowdhury, J.E.Berleman, and C.E.Bauer (2011).
Cyclic GMP controls Rhodospirillum centenum cyst development.
  Mol Microbiol, 79, 600-615.  
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.  
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.  
19594171 A.J.Lee, R.W.Clark, H.Youn, S.Ponter, and J.N.Burstyn (2009).
Guanidine hydrochloride-induced unfolding of the three heme coordination states of the CO-sensing transcription factor, CooA.
  Biochemistry, 48, 6585-6597.  
19132361 A.V.Nair, C.Anselmi, and M.Mazzolini (2009).
Movements of native C505 during channel gating in CNGA1 channels.
  Eur Biophys J, 38, 465-478.  
19714199 B.A.Kidd, D.Baker, and W.E.Thomas (2009).
Computation of conformational coupling in allosteric proteins.
  PLoS Comput Biol, 5, e1000484.  
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.  
19193643 D.T.Gallagher, N.Smith, S.K.Kim, H.Robinson, and P.T.Reddy (2009).
Profound Asymmetry in the Structure of the cAMP-free cAMP Receptor Protein (CRP) from Mycobacterium tuberculosis.
  J Biol Chem, 284, 8228-8232.  
  19309730 J.E.Seedorff, M.E.Rodgers, and R.Schleif (2009).
Opposite allosteric mechanisms in TetR and CAP.
  Protein Sci, 18, 775-781.  
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
19359484 N.Popovych, S.R.Tzeng, M.Tonelli, R.H.Ebright, and C.G.Kalodimos (2009).
Structural basis for cAMP-mediated allosteric control of the catabolite activator protein.
  Proc Natl Acad Sci U S A, 106, 6927-6932.
PDB code: 2wc2
19924217 S.R.Tzeng, and C.G.Kalodimos (2009).
Dynamic activation of an allosteric regulatory protein.
  Nature, 462, 368-372.  
18599828 C.D.Doern, R.C.Holder, and S.D.Reid (2008).
Point mutations within the streptococcal regulator of virulence (Srv) alter protein-DNA interactions and Srv function.
  Microbiology, 154, 1998-2007.  
18717788 C.Levy, K.Pike, D.J.Heyes, M.G.Joyce, K.Gabor, H.Smidt, J.van der Oost, and D.Leys (2008).
Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulator.
  Mol Microbiol, 70, 151-167.
PDB codes: 3e5q 3e5u 3e5x 3e6b 3e6c 3e6d
18456811 H.Youn, J.Koh, and G.P.Roberts (2008).
Two-state allosteric modeling suggests protein equilibrium as an integral component for cyclic AMP (cAMP) specificity in the cAMP receptor protein of Escherichia coli.
  J Bacteriol, 190, 4532-4540.  
18699868 Y.Agari, A.Kashihara, S.Yokoyama, S.Kuramitsu, and A.Shinkai (2008).
Global gene expression mediated by Thermus thermophilus SdrP, a CRP/FNR family transcriptional regulator.
  Mol Microbiol, 70, 60-75.
PDB code: 2zcw
17531094 A.Del Sol, M.J.Araúzo-Bravo, D.Amoros, and R.Nussinov (2007).
Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages.
  Genome Biol, 8, R92.  
17369302 A.Shinkai, S.Kira, N.Nakagawa, A.Kashihara, S.Kuramitsu, and S.Yokoyama (2007).
Transcription activation mediated by a cyclic AMP receptor protein from Thermus thermophilus HB8.
  J Bacteriol, 189, 3891-3901.  
17505875 E.Fic, A.Górecki, and Z.Wasylewski (2007).
Fluorescence quenching studies of conformational changes induced by cAMP and DNA binding to heterodimer of cyclic AMP receptor protein from Escherichia coli.
  Protein J, 26, 457-466.  
17158453 H.Youn, R.L.Kerby, J.Koh, and G.P.Roberts (2007).
A C-helix residue, Arg-123, has important roles in both the active and inactive forms of the cAMP receptor protein.
  J Biol Chem, 282, 3632-3639.  
17687489 J.Kong, and S.Yu (2007).
Fourier transform infrared spectroscopic analysis of protein secondary structures.
  Acta Biochim Biophys Sin (Shanghai), 39, 549-559.  
17327664 M.Borjigin, H.Li, N.D.Lanz, R.L.Kerby, G.P.Roberts, and T.L.Poulos (2007).
Structure-based hypothesis on the activation of the CO-sensing transcription factor CooA.
  Acta Crystallogr D Biol Crystallogr, 63, 282-287.
PDB code: 2hkx
17720248 M.Ibrahim, M.Kuchinskas, H.Youn, R.L.Kerby, G.P.Roberts, T.L.Poulos, and T.G.Spiro (2007).
Mechanism of the CO-sensing heme protein CooA: new insights from the truncated heme domain and UVRR spectroscopy.
  J Inorg Biochem, 101, 1776-1785.  
17074757 R.Das, and G.Melacini (2007).
A model for agonism and antagonism in an ancient and ubiquitous cAMP-binding domain.
  J Biol Chem, 282, 581-593.  
17182741 R.Das, V.Esposito, M.Abu-Abed, G.S.Anand, S.S.Taylor, and G.Melacini (2007).
cAMP activation of PKA defines an ancient signaling mechanism.
  Proc Natl Acad Sci U S A, 104, 93-98.  
17933899 T.J.Kim, S.Chauhan, V.L.Motin, E.B.Goh, M.M.Igo, and G.M.Young (2007).
Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein.
  J Bacteriol, 189, 8890-8900.  
16796679 H.Reents, I.Gruner, U.Harmening, L.H.Böttger, G.Layer, P.Heathcote, A.X.Trautwein, D.Jahn, and E.Härtig (2006).
Bacillus subtilis Fnr senses oxygen via a [4Fe-4S] cluster coordinated by three cysteine residues without change in the oligomeric state.
  Mol Microbiol, 60, 1432-1445.  
16260780 H.Youn, R.L.Kerby, M.Conrad, and G.P.Roberts (2006).
Study of highly constitutively active mutants suggests how cAMP activates cAMP receptor protein.
  J Biol Chem, 281, 1119-1127.  
16959764 L.J.Moore, E.L.Mettert, and P.J.Kiley (2006).
Regulation of FNR dimerization by subunit charge repulsion.
  J Biol Chem, 281, 33268-33275.  
  16946467 M.Akif, Y.Akhter, S.E.Hasnain, and S.C.Mande (2006).
Crystallization and preliminary X-ray crystallographic studies of Mycobacterium tuberculosis CRP/FNR family transcription regulator.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 873-875.  
16500960 M.Berrera, S.Pantano, and P.Carloni (2006).
cAMP Modulation of the cytoplasmic domain in the HCN2 channel investigated by molecular simulations.
  Biophys J, 90, 3428-3433.  
16803881 M.G.Joyce, C.Levy, K.Gábor, S.M.Pop, B.D.Biehl, T.I.Doukov, J.M.Ryter, H.Mazon, H.Smidt, R.H.van den Heuvel, S.W.Ragsdale, J.van der Oost, and D.Leys (2006).
CprK crystal structures reveal mechanism for transcriptional control of halorespiration.
  J Biol Chem, 281, 28318-28325.
PDB codes: 2h6b 2h6c
16873369 M.Ibrahim, R.L.Kerby, M.Puranik, I.H.Wasbotten, H.Youn, G.P.Roberts, and T.G.Spiro (2006).
Heme displacement mechanism of CooA activation: mutational and Raman spectroscopic evidence.
  J Biol Chem, 281, 29165-29173.  
16439368 M.Kubo, S.Inagaki, S.Yoshioka, T.Uchida, Y.Mizutani, S.Aono, and T.Kitagawa (2006).
Evidence for displacements of the C-helix by CO ligation and DNA binding to CooA revealed by UV resonance Raman spectroscopy.
  J Biol Chem, 281, 11271-11278.  
16906160 N.Popovych, S.Sun, R.H.Ebright, and C.G.Kalodimos (2006).
Dynamically driven protein allostery.
  Nat Struct Mol Biol, 13, 831-838.  
15618393 H.M.Berman, L.F.Ten Eyck, D.S.Goodsell, N.M.Haste, A.Kornev, and S.S.Taylor (2005).
The cAMP binding domain: an ancient signaling module.
  Proc Natl Acad Sci U S A, 102, 45-50.  
15805503 H.Youn, M.V.Thorsteinsson, M.Conrad, R.L.Kerby, and G.P.Roberts (2005).
Dual roles of an E-helix residue, Glu167, in the transcriptional activator function of CooA.
  J Bacteriol, 187, 2573-2581.  
15813735 M.Eiting, G.Hagelüken, W.D.Schubert, and D.W.Heinz (2005).
The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif.
  Mol Microbiol, 56, 433-446.
PDB codes: 2beo 2bgc
15720385 M.Tworzydło, A.Polit, J.Mikołajczak, and Z.Wasylewski (2005).
Fluorescence quenching and kinetic studies of conformational changes induced by DNA and cAMP binding to cAMP receptor protein from Escherichia coli.
  FEBS J, 272, 1103-1116.  
15102444 C.L.Lawson, D.Swigon, K.S.Murakami, S.A.Darst, H.M.Berman, and R.H.Ebright (2004).
Catabolite activator protein: DNA binding and transcription activation.
  Curr Opin Struct Biol, 14, 10-20.  
15550244 G.M.Clayton, W.R.Silverman, L.Heginbotham, and J.H.Morais-Cabral (2004).
Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel.
  Cell, 119, 615-627.
PDB codes: 1u12 1vp6
15353565 G.P.Roberts, H.Youn, and R.L.Kerby (2004).
CO-sensing mechanisms.
  Microbiol Mol Biol Rev, 68, 453-473.  
14973040 H.Youn, R.L.Kerby, M.Conrad, and G.P.Roberts (2004).
Functionally critical elements of CooA-related CO sensors.
  J Bacteriol, 186, 1320-1329.  
15326178 T.Yamashita, Y.Hoashi, Y.Tomisugi, Y.Ishikawa, and T.Uno (2004).
The C-helix in CooA rolls upon CO binding to ferrous heme.
  J Biol Chem, 279, 47320-47325.  
15186408 Y.Vega, M.Rauch, M.J.Banfield, S.Ermolaeva, M.Scortti, W.Goebel, and J.A.Vázquez-Boland (2004).
New Listeria monocytogenes prfA* mutants, transcriptional properties of PrfA* proteins and structure-function of the virulence regulator PrfA.
  Mol Microbiol, 52, 1553-1565.  
12939272 A.Polit, P.Bonarek, B.Kepys, S.Kedracka-Krok, A.Górecki, and Z.Wasylewski (2003).
Kinetic studies of cAMP-induced allosteric changes in mutants T127I, S128A, and T127I/S128A of the cAMP receptor protein from Escherichia coli.
  J Biol Chem, 278, 43020-43026.  
12653996 A.Polit, U.Błaszczyk, and Z.Wasylewski (2003).
Steady-state and time-resolved fluorescence studies of conformational changes induced by cyclic AMP and DNA binding to cyclic AMP receptor protein from Escherichia coli.
  Eur J Biochem, 270, 1413-1423.  
12796503 C.M.Coyle, M.Puranik, H.Youn, S.B.Nielsen, R.D.Williams, R.L.Kerby, G.P.Roberts, and T.G.Spiro (2003).
Activation mechanism of the CO sensor CooA. Mutational and resonance Raman spectroscopic studies.
  J Biol Chem, 278, 35384-35393.  
12433917 H.Youn, R.L.Kerby, and G.P.Roberts (2003).
The role of the hydrophobic distal heme pocket of CooA in ligand sensing and response.
  J Biol Chem, 278, 2333-2340.  
12866047 M.Punta, A.Cavalli, V.Torre, and P.Carloni (2003).
Molecular modeling studies on CNG channel from bovine retinal rod: a structural model of the cyclic nucleotide-binding domain.
  Proteins, 52, 332-338.  
12551924 R.Chen, and J.C.Lee (2003).
Functional roles of loops 3 and 4 in the cyclic nucleotide binding domain of cyclic AMP receptor protein from Escherichia coli.
  J Biol Chem, 278, 13235-13243.  
12022869 A.Dong, J.M.Malecki, L.Lee, J.F.Carpenter, and J.C.Lee (2002).
Ligand-induced conformational and structural dynamics changes in Escherichia coli cyclic AMP receptor protein.
  Biochemistry, 41, 6660-6667.  
12429832 L.Bosgraaf, H.Russcher, H.Snippe, S.Bader, J.Wind, and P.J.Van Haastert (2002).
Identification and characterization of two unusual cGMP-stimulated phoshodiesterases in dictyostelium.
  Mol Biol Cell, 13, 3878-3889.  
12198158 L.Bosgraaf, H.Russcher, J.L.Smith, D.Wessels, D.R.Soll, and P.J.Van Haastert (2002).
A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis in Dictyostelium.
  EMBO J, 21, 4560-4570.  
12496096 M.Mazzolini, M.Punta, and V.Torre (2002).
Movement of the C-helix during the gating of cyclic nucleotide-gated channels.
  Biophys J, 83, 3283-3295.  
12124274 N.Bennett, M.Ildefonse, F.Pagès, and M.Ragno (2002).
Gating of heteromeric retinal rod channels by cyclic AMP: role of the C-terminal and pore domains.
  Biophys J, 83, 920-931.  
11979597 N.Fujimoto, A.Toyama, and H.Takeuchi (2002).
Binding modes of cyclic AMP and environments of tryptophan residues in 1:1 and 1:2 complexes of cyclic AMP receptor protein and cyclic AMP.
  Biopolymers, 67, 186-196.  
12057955 S.A.Beatson, C.B.Whitchurch, J.L.Sargent, R.C.Levesque, and J.S.Mattick (2002).
Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa.
  J Bacteriol, 184, 3605-3613.  
11863432 S.H.Lin, L.Kovac, A.J.Chin, C.C.Chin, and J.C.Lee (2002).
Ability of E. coli cyclic AMP receptor protein to differentiate cyclic nucelotides: effects of single site mutations.
  Biochemistry, 41, 2946-2955.  
11343786 J.G.Harman (2001).
Allosteric regulation of the cAMP receptor protein.
  Biochim Biophys Acta, 1547, 1.  
11522788 J.Leduc, M.V.Thorsteinsson, T.Gaal, and G.P.Roberts (2001).
Mapping CooA.RNA polymerase interactions. Identification of activating regions 2 and 3 in CooA, the co-sensing transcriptional activator.
  J Biol Chem, 276, 39968-39973.  
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.