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Transferase PDB id
1f51
Jmol
Contents
Protein chains
181 a.a. *
119 a.a. *
Metals
_MG ×3
* Residue conservation analysis
PDB id:
1f51
Name: Transferase
Title: A transient interaction between two phosphorelay proteins trapped in a crystal lattice reveals the mechanism of molecular recognition and phosphotransfer in singal transduction
Structure: Sporulation initiation phosphotransferase b. Chain: a, b, c, d. Engineered: yes. Sporulation initiation phosphotransferase f. Chain: e, f, g, h. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423.
Biol. unit: Tetramer (from PQS)
Resolution:
3.00Å     R-factor:   0.228     R-free:   0.268
Authors: J.Zapf,U.Sen,M.Madhusudan,J.A.Hoch,K.I.Varughese
Key ref:
J.Zapf et al. (2000). A transient interaction between two phosphorelay proteins trapped in a crystal lattice reveals the mechanism of molecular recognition and phosphotransfer in signal transduction. Structure, 8, 851-862. PubMed id: 10997904 DOI: 10.1016/S0969-2126(00)00174-X
Date:
11-Jun-00     Release date:   23-Aug-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam  
P06535  (SP0B_BACSU) -  Sporulation initiation phosphotransferase B
Seq:
Struc: 		192 a.a.
181 a.a.
Protein chains
Pfam   ArchSchema ?
P06628  (SP0F_BACSU) -  Sporulation initiation phosphotransferase F
Seq:
Struc: 		124 a.a.
119 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     response to stimulus   6 terms 
  Biochemical function     transferase activity     6 terms  

 

 
DOI no: 10.1016/S0969-2126(00)00174-X Structure 8:851-862 (2000)
PubMed id: 10997904  
 
 
A transient interaction between two phosphorelay proteins trapped in a crystal lattice reveals the mechanism of molecular recognition and phosphotransfer in signal transduction.
J.Zapf, U.Sen, Madhusudan, J.A.Hoch, K.I.Varughese.
 
  ABSTRACT  
 
BACKGROUND: Spo0F and Spo0B specifically exchange a phosphoryl group in a central step of the phosphorelay signal transduction system that controls sporulation in Bacilli. Spo0F belongs to the superfamily of response regulator proteins and is one of 34 such proteins in Bacillus subtilis. Spo0B is structurally similar to the phosphohistidine domain of histidine kinases, such as EnvZ, and exchanges a phosphoryl group between His30 and Asp54 on Spo0F. Information at the molecular level on the interaction between response regulators and phosphohistidine domains is necessary to develop a rationale for how phospho-signaling fidelity is maintained in two-component systems. RESULTS: Structural analysis of a co-crystal of the Spo0F response regulator interacting with the Spo0B phosphotransferase of the phosphorelay signal transduction system of B. subtilis was carried out using X-ray crystallographic techniques. The association of the two molecules brings the catalytic residues from both proteins into precise alignment for phosphoryltransfer. Upon complex formation, the Spo0B conformation remains unchanged. Spo0F also retains the overall conformation; however, two loops around the active site show significant deviations. CONCLUSIONS: The Spo0F-Spo0B interaction appears to be a prototype for response regulator-histidine kinase interactions. The primary contact surface between these two proteins is formed by hydrophobic regions in both proteins. The Spo0F residues making up the hydrophobic patch are very similar in all response regulators suggesting that the binding is initiated through the same residues in all interacting response regulator-kinase pairs. The bulk of the interactions outside this patch are through nonconserved residues. Recognition specificity is proposed to arise from interactions of the nonconserved residues, especially the hypervariable residues of the beta4-alpha4 loop.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. 2 F[o]-F[c] map of the active-site region contoured at the 1s level. The position of Mg2+ is shown as a black dot.
 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 851-862) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21401736 E.Steiner, A.E.Dago, D.I.Young, J.T.Heap, N.P.Minton, J.A.Hoch, and M.Young (2011).
Multiple orphan histidine kinases interact directly with Spo0A to control the initiation of endospore formation in Clostridium acetobutylicum.
  Mol Microbiol, 80, 641-654.  
21481780 K.Schmöe, V.V.Rogov, N.Y.Rogova, F.Löhr, P.Güntert, F.Bernhard, and V.Dötsch (2011).
Structural Insights into Rcs Phosphotransfer: The Newly Identified RcsD-ABL Domain Enhances Interaction with the Response Regulator RcsB.
  Structure, 19, 577-587.
PDB code: 2kx7
21179024 A.Siryaporn, B.S.Perchuk, M.T.Laub, and M.Goulian (2010).
Evolving a robust signal transduction pathway from weak cross-talk.
  Mol Syst Biol, 6, 452.  
20161720 C.H.Bell, S.L.Porter, A.Strawson, D.I.Stuart, and J.P.Armitage (2010).
Using structural information to change the phosphotransfer specificity of a two-component chemotaxis signalling complex.
  PLoS Biol, 8, e1000306.
PDB codes: 3kyi 3kyj
20133181 H.Szurmant, and J.A.Hoch (2010).
Interaction fidelity in two-component signaling.
  Curr Opin Microbiol, 13, 190-197.  
20117042 R.C.Stewart (2010).
Protein histidine kinases: assembly of active sites and their regulation in signaling pathways.
  Curr Opin Microbiol, 13, 133-141.  
20825354 T.Krell, J.Lacal, A.Busch, H.Silva-Jiménez, M.E.Guazzaroni, and J.L.Ramos (2010).
Bacterial sensor kinases: diversity in the recognition of environmental signals.
  Annu Rev Microbiol, 64, 539-559.  
19503843 A.Chakicherla, C.L.Ecale Zhou, M.L.Dang, V.Rodriguez, J.N.Hansen, and A.Zemla (2009).
SpaK/SpaR two-component system characterized by a structure-driven domain-fusion method and in vitro phosphorylation studies.
  PLoS Comput Biol, 5, e1000401.  
19259771 D.Ortiz de Orué Lucana, and M.R.Groves (2009).
The three-component signalling system HbpS-SenS-SenR as an example of a redox sensing pathway in bacteria.
  Amino Acids, 37, 479-486.  
19004019 G.H.Peters (2009).
The effect of Asp54 phosphorylation on the energetics and dynamics in the response regulator protein Spo0F studied by molecular dynamics.
  Proteins, 75, 648-658.  
19101565 M.J.Bick, V.Lamour, K.R.Rajashankar, Y.Gordiyenko, C.V.Robinson, and S.A.Darst (2009).
How to switch off a histidine kinase: crystal structure of Geobacillus stearothermophilus KinB with the inhibitor Sda.
  J Mol Biol, 386, 163-177.
PDB code: 3d36
19116270 M.Weigt, R.A.White, H.Szurmant, J.A.Hoch, and T.Hwa (2009).
Identification of direct residue contacts in protein-protein interaction by message passing.
  Proc Natl Acad Sci U S A, 106, 67-72.  
19800110 P.Casino, V.Rubio, and A.Marina (2009).
Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction.
  Cell, 139, 325-336.
PDB codes: 3dge 3dgf 3gl9
19575571 R.Gao, and A.M.Stock (2009).
Biological insights from structures of two-component proteins.
  Annu Rev Microbiol, 63, 133-154.  
19246748 R.Shrivastava, A.K.Ghosh, and A.K.Das (2009).
Intra- and intermolecular domain interactions among novel two-component system proteins coded by Rv0600c, Rv0601c and Rv0602c of Mycobacterium tuberculosis.
  Microbiology, 155, 772-779.  
18588317 H.Szurmant, B.G.Bobay, R.A.White, D.M.Sullivan, R.J.Thompson, T.Hwa, J.A.Hoch, and J.Cavanagh (2008).
Co-evolving motions at protein-protein interfaces of two-component signaling systems identified by covariance analysis.
  Biochemistry, 47, 7782-7784.  
18555780 J.M.Skerker, B.S.Perchuk, A.Siryaporn, E.A.Lubin, O.Ashenberg, M.Goulian, and M.T.Laub (2008).
Rewiring the specificity of two-component signal transduction systems.
  Cell, 133, 1043-1054.  
18277381 L.Burger, and E.van Nimwegen (2008).
Accurate prediction of protein-protein interactions from sequence alignments using a Bayesian method.
  Mol Syst Biol, 4, 165.  
18694439 R.B.Bourret (2008).
Signal transduction meets systems biology: deciphering specificity determinants for protein-protein interactions.
  Mol Microbiol, 69, 1336-1340.  
18713030 R.P.Novick, and E.Geisinger (2008).
Quorum sensing in staphylococci.
  Annu Rev Genet, 42, 541-564.  
18455986 R.Paul, T.Jaeger, S.Abel, I.Wiederkehr, M.Folcher, E.G.Biondi, M.T.Laub, and U.Jenal (2008).
Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate.
  Cell, 133, 452-461.  
18076904 X.Zhao, D.M.Copeland, A.S.Soares, and A.H.West (2008).
Crystal structure of a complex between the phosphorelay protein YPD1 and the response regulator domain of SLN1 bound to a phosphoryl analog.
  J Mol Biol, 375, 1141-1151.
PDB code: 2r25
18076326 M.T.Laub, and M.Goulian (2007).
Specificity in two-component signal transduction pathways.
  Annu Rev Genet, 41, 121-145.  
17322531 T.Gao, X.Zhang, N.B.Ivleva, S.S.Golden, and A.LiWang (2007).
NMR structure of the pseudo-receiver domain of CikA.
  Protein Sci, 16, 465-475.
PDB code: 2j48
16430694 A.Howell, S.Dubrac, D.Noone, K.I.Varughese, and K.Devine (2006).
Interactions between the YycFG and PhoPR two-component systems in Bacillus subtilis: the PhoR kinase phosphorylates the non-cognate YycF response regulator upon phosphate limitation.
  Mol Microbiol, 59, 1199-1215.  
16788205 K.I.Varughese, I.Tsigelny, and H.Zhao (2006).
The crystal structure of beryllofluoride Spo0F in complex with the phosphotransferase Spo0B represents a phosphotransfer pretransition state.
  J Bacteriol, 188, 4970-4977.
PDB code: 2ftk
16420367 K.Wörner, H.Szurmant, C.Chiang, and J.A.Hoch (2006).
Phosphorylation and functional analysis of the sporulation initiation factor Spo0A from Clostridium botulinum.
  Mol Microbiol, 59, 1000-1012.  
17001075 R.Grenha, N.J.Rzechorzek, J.A.Brannigan, R.N.de Jong, E.Ab, T.Diercks, V.Truffault, J.C.Ladds, M.J.Fogg, C.Bongiorni, M.Perego, R.Kaptein, K.S.Wilson, G.E.Folkers, and A.J.Wilkinson (2006).
Structural characterization of Spo0E-like protein-aspartic acid phosphatases that regulate sporulation in bacilli.
  J Biol Chem, 281, 37993-38003.
PDB codes: 2bzb 2c0s
16319927 A.Marina, C.D.Waldburger, and W.A.Hendrickson (2005).
Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein.
  EMBO J, 24, 4247-4259.
PDB code: 2c2a
16333746 D.J.Kojetin, R.J.Thompson, L.M.Benson, S.Naylor, J.Waterman, K.G.Davies, C.H.Opperman, K.Stephenson, J.A.Hoch, and J.Cavanagh (2005).
Structural analysis of divalent metals binding to the Bacillus subtilis response regulator Spo0F: the possibility for in vitro metalloregulation in the initiation of sporulation.
  Biometals, 18, 449-466.  
15808745 K.Stephenson, and R.J.Lewis (2005).
Molecular insights into the initiation of sporulation in Gram-positive bacteria: new technologies for an old phenomenon.
  FEMS Microbiol Rev, 29, 281-301.  
15880257 X.H.Cai, Q.Zhang, S.Y.Shi, and D.F.Ding (2005).
Searching for potential drug targets in two-component and phosphorelay signal-transduction systems using three-dimensional cluster analysis.
  Acta Biochim Biophys Sin (Shanghai), 37, 293-302.  
15039551 D.Mukhopadhyay, U.Sen, J.Zapf, and K.I.Varughese (2004).
Metals in the sporulation phosphorelay: manganese binding by the response regulator Spo0F.
  Acta Crystallogr D Biol Crystallogr, 60, 638-645.
PDB code: 1pey
15255896 K.Muchová, R.J.Lewis, D.Perecko, J.A.Brannigan, J.C.Ladds, A.Leech, A.J.Wilkinson, and I.Barák (2004).
Dimer-induced signal propagation in Spo0A.
  Mol Microbiol, 53, 829-842.  
15023339 S.L.Rowland, W.F.Burkholder, K.A.Cunningham, M.W.Maciejewski, A.D.Grossman, and G.F.King (2004).
Structure and mechanism of action of Sda, an inhibitor of the histidine kinases that regulate initiation of sporulation in Bacillus subtilis.
  Mol Cell, 13, 689-701.
PDB code: 1pv0
12829280 J.C.Ladds, K.Muchová, D.Blaskovic, R.J.Lewis, J.A.Brannigan, A.J.Wilkinson, and I.Barák (2003).
The response regulator Spo0A from Bacillus subtilis is efficiently phosphorylated in Escherichia coli.
  FEMS Microbiol Lett, 223, 153-157.  
  12915093 J.J.Bijlsma, and E.A.Groisman (2003).
Making informed decisions: regulatory interactions between two-component systems.
  Trends Microbiol, 11, 359-366.  
12679523 L.Li, E.I.Shakhnovich, and L.A.Mirny (2003).
Amino acids determining enzyme-substrate specificity in prokaryotic and eukaryotic protein kinases.
  Proc Natl Acad Sci U S A, 100, 4463-4468.  
12754242 L.Qin, S.Cai, Y.Zhu, and M.Inouye (2003).
Cysteine-scanning analysis of the dimerization domain of EnvZ, an osmosensing histidine kinase.
  J Bacteriol, 185, 3429-3435.  
12702718 M.E.Castelli, A.Cauerhff, M.Amongero, F.C.Soncini, and E.G.Vescovi (2003).
The H box-harboring domain is key to the function of the Salmonella enterica PhoQ Mg2+-sensor in the recognition of its partner PhoP.
  J Biol Chem, 278, 23579-23585.  
12867451 N.Ohta, and A.Newton (2003).
The core dimerization domains of histidine kinases contain recognition specificity for the cognate response regulator.
  J Bacteriol, 185, 4424-4431.  
12582120 S.W.Porter, Q.Xu, and A.H.West (2003).
Ssk1p response regulator binding surface on histidine-containing phosphotransfer protein Ypd1p.
  Eukaryot Cell, 2, 27-33.  
12406209 K.Stephenson, and J.A.Hoch (2002).
Evolution of signalling in the sporulation phosphorelay.
  Mol Microbiol, 46, 297-304.  
  12191621 K.Stephenson, and J.A.Hoch (2002).
Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy.
  Pharmacol Ther, 93, 293-305.  
12208995 R.Hengge-Aronis (2002).
Signal transduction and regulatory mechanisms involved in control of the sigma(S) (RpoS) subunit of RNA polymerase.
  Microbiol Mol Biol Rev, 66, 373.  
12080332 R.Zhao, E.J.Collins, R.B.Bourret, and R.E.Silversmith (2002).
Structure and catalytic mechanism of the E. coli chemotaxis phosphatase CheZ.
  Nat Struct Biol, 9, 570-575.
PDB code: 1kmi
12067336 S.J.Stephenson, and M.Perego (2002).
Interaction surface of the Spo0A response regulator with the Spo0E phosphatase.
  Mol Microbiol, 44, 1455-1467.  
12453214 T.Yoshida, L.Qin, and M.Inouye (2002).
Formation of the stoichiometric complex of EnvZ, a histidine kinase, with its response regulator, OmpR.
  Mol Microbiol, 46, 1273-1282.  
11442836 E.Klauck, M.Lingnau, and R.Hengge-Aronis (2001).
Role of the response regulator RssB in sigma recognition and initiation of sigma proteolysis in Escherichia coli.
  Mol Microbiol, 40, 1381-1390.  
11489844 J.A.Hoch, and K.I.Varughese (2001).
Keeping signals straight in phosphorelay signal transduction.
  J Bacteriol, 183, 4941-4949.  
11121774 A.L.Sonenshein (2000).
Control of sporulation initiation in Bacillus subtilis.
  Curr Opin Microbiol, 3, 561-566.  
11069677 M.Jiang, W.Shao, M.Perego, and J.A.Hoch (2000).
Multiple histidine kinases regulate entry into stationary phase and sporulation in Bacillus subtilis.
  Mol Microbiol, 38, 535-542.  
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 code is shown on the right.