PDBsum entry 1g4w

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protein links
Signaling protein PDB id
Protein chain
341 a.a. *
Waters ×154
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Crystal structure of the salmonella tyrosine phosphatase and gtpase activating protein sptp
Structure: Protein tyrosine phosphatase sptp. Chain: r. Fragment: sptp residues 161-543. Engineered: yes
Source: Salmonella typhimurium. Organism_taxid: 602. Gene: sptp. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
2.20Å     R-factor:   0.260     R-free:   0.314
Authors: C.E.Stebbins,J.E.Galan
Key ref:
C.E.Stebbins and J.E.Galán (2000). Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol Cell, 6, 1449-1460. PubMed id: 11163217 DOI: 10.1016/S1097-2765(00)00141-6
28-Oct-00     Release date:   24-Jan-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P74873  (SPTP_SALTY) -  Secreted effector protein SptP
543 a.a.
341 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     2 terms  


DOI no: 10.1016/S1097-2765(00)00141-6 Mol Cell 6:1449-1460 (2000)
PubMed id: 11163217  
Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1.
C.E.Stebbins, J.E.Galán.
Salmonella spp. utilize a specialized protein secretion system to deliver a battery of effector proteins into host cells. Several of these effectors stimulate Cdc42- and Rac1-dependent cytoskeletal changes that promote bacterial internalization. These potentially cytotoxic alterations are rapidly reversed by the effector SptP, a tyrosine phosphatase and GTPase activating protein (GAP) that targets Cdc42 and Rac1. The 2.3 A resolution crystal structure of an SptP-Rac1 transition state complex reveals an unusual GAP architecture that mimics host functional homologs. The phosphatase domain possesses a conserved active site but distinct surface properties. Binding to Rac1 induces a dramatic stabilization in SptP of a four-helix bundle that makes extensive contacts with the Switch I and Switch II regions of the GTPase.
  Selected figure(s)  
Figure 4.
Figure 4. The Interface with Rac1 Is Extensive and Highly Complementary to the Switch I, Switch II, and Nucleotide Regions of the GTPase(A) The extensive surface charge complementarity between the GAP domain and Rac1 is illustrated with a molecular surface colored by electrostatic potential such that red is negative (acidic) and blue is positive (basic). Arrows indicate regions of charge complementarity between the Rac1 and SptP surfaces. (B and C) The SptP GAP domain (secondary structure shown in blue and side chains in cyan) interact with the Switch I (yellow) and Switch II (red) regulatory elements of Rac1 (with yellow side chains). Hydrogen bonds are indicated by white dotted lines, and the atoms of nitrogen and oxygen are show in blue and red, respectively. Water molecules are shown as large magenta spheres. A large “W” indicates the nucleophilic water molecule positioned by Gln-61 of Rac. (D) SptP positions Gln-61 of Rac1 through molecular contacts and inserts Arg-209 into the active site to stabilize the transition state. Hydrogen bonds are indicated by white dotted lines or as smaller gray dotted lines for weak bonds. AlF[3] is shown with the fluorides colored brown and the aluminum gray. The magnesium ion and water molecules are shown as large blue or magenta spheres, respectively. GDP carbon bonds are shown in yellow. A large “W” indicates the nucleophilic water molecule positioned by Gln-61 of Rac1. The phosphate binding (P loop) and guanine binding loops (G loops) of Rac1 are shown in purple. The bonds proposed to form during the phosphoryl transfer are shown as solid white lines. (E) The interface between the GAP (blue) and tyrosine phosphatase (purple) domains of SptP consists of several direct and water-mediated hydrogen bonds as well as a small hydrophobic interface.
Figure 5.
Figure 5. The GAP Domain of SptP Undergoes Marked Structural Changes upon Binding Rac1A comparison of the atomic B factors between the SptP monomer and the SptP–Rac1 heterodimeric transition state complex is shown. The ribbon diagrams are colored according to an absolute gradient in the B factor from blue (ordered with a low B factor) through red (disordered with a high B factor). Connectivity missing due to disorder in the monomer is represented by black dotted lines based on their conformation in the heterodimer.
  The above figures are reprinted by permission from Cell Press: Mol Cell (2000, 6, 1449-1460) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21534865 Y.Litvak, R.Levin-Klein, M.Avner, and Z.Selinger (2011).
High catalytic efficiency and resistance to denaturing in bacterial Rho GTPase-activating proteins.
  Biol Chem, 392, 505-516.  
19793077 I.Yeam, H.P.Nguyen, and G.B.Martin (2010).
Phosphorylation of the Pseudomonas syringae effector AvrPto is required for FLS2/BAK1-independent virulence activity and recognition by tobacco.
  Plant J, 61, 16-24.  
19680249 A.R.Hauser (2009).
The type III secretion system of Pseudomonas aeruginosa: infection by injection.
  Nat Rev Microbiol, 7, 654-665.  
  19286132 D.Humphreys, P.J.Hume, and V.Koronakis (2009).
The Salmonella effector SptP dephosphorylates host AAA+ ATPase VCP to promote development of its intracellular replicative niche.
  Cell Host Microbe, 5, 225-233.  
  19527884 J.E.Galán (2009).
Common themes in the design and function of bacterial effectors.
  Cell Host Microbe, 5, 571-579.  
19033377 K.H.Nielsen, H.Chamieh, C.B.Andersen, F.Fredslund, K.Hamborg, H.Le Hir, and G.R.Andersen (2009).
Mechanism of ATP turnover inhibition in the EJC.
  RNA, 15, 67-75.
PDB code: 3ex7
19806153 N.C.Elde, and H.S.Malik (2009).
The evolutionary conundrum of pathogen mimicry.
  Nat Rev Microbiol, 7, 787-797.  
18216259 M.A.Fischbach, C.T.Walsh, and J.Clardy (2008).
The evolution of gene collectives: How natural selection drives chemical innovation.
  Proc Natl Acad Sci U S A, 105, 4601-4608.  
17452788 G.Prehna, and C.E.Stebbins (2007).
A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium.
  Acta Crystallogr D Biol Crystallogr, 63, 628-635.
PDB code: 2p2l
17593246 K.T.Ly, and J.E.Casanova (2007).
Mechanisms of Salmonella entry into host cells.
  Cell Microbiol, 9, 2103-2111.  
17097678 M.Sommerhalter, Y.Zhang, and A.C.Rosenzweig (2007).
Solution structure of the COMMD1 N-terminal domain.
  J Mol Biol, 365, 715-721.
PDB code: 2h2m
17662586 S.Mattoo, Y.M.Lee, and J.E.Dixon (2007).
Interactions of bacterial effector proteins with host proteins.
  Curr Opin Immunol, 19, 392-401.  
17237181 Y.Litvak, and Z.Selinger (2007).
Aeromonas salmonicida toxin AexT has a Rho family GTPase-activating protein domain.
  J Bacteriol, 189, 2558-2560.  
16356724 A.Wittinghofer (2006).
Phosphoryl transfer in Ras proteins, conclusive or elusive?
  Trends Biochem Sci, 31, 20-23.  
16713730 D.Desveaux, A.U.Singer, and J.L.Dangl (2006).
Type III effector proteins: doppelgangers of bacterial virulence.
  Curr Opin Plant Biol, 9, 376-382.  
17136086 J.E.Galán, and H.Wolf-Watz (2006).
Protein delivery into eukaryotic cells by type III secretion machines.
  Nature, 444, 567-573.  
16988261 L.M.Chen, G.Briones, R.O.Donis, and J.E.Galán (2006).
Optimization of the delivery of heterologous proteins by the Salmonella enterica serovar Typhimurium type III secretion system for vaccine development.
  Infect Immun, 74, 5826-5833.  
16681842 M.Aili, E.L.Isaksson, B.Hallberg, H.Wolf-Watz, and R.Rosqvist (2006).
Functional analysis of the YopE GTPase-activating protein (GAP) activity of Yersinia pseudotuberculosis.
  Cell Microbiol, 8, 1020-1033.  
16243562 R.S.Rudrabhatla, S.K.Selvaraj, and N.V.Prasadarao (2006).
Role of Rac1 in Escherichia coli K1 invasion of human brain microvascular endothelial cells.
  Microbes Infect, 8, 460-469.  
16098211 C.E.Stebbins (2005).
Structural microbiology at the pathogen-host interface.
  Cell Microbiol, 7, 1227-1236.  
15694851 J.C.Patel, and J.E.Galán (2005).
Manipulation of the host actin cytoskeleton by Salmonella--all in the name of entry.
  Curr Opin Microbiol, 8, 10-15.  
16182381 J.C.Patel, O.W.Rossanese, and J.E.Galán (2005).
The functional interface between Salmonella and its host cell: opportunities for therapeutic intervention.
  Trends Pharmacol Sci, 26, 564-570.  
16153847 S.Sikora, A.Strongin, and A.Godzik (2005).
Convergent evolution as a mechanism for pathogenic adaptation.
  Trends Microbiol, 13, 522-527.  
16208377 Y.Akeda, and J.E.Galán (2005).
Chaperone release and unfolding of substrates in type III secretion.
  Nature, 437, 911-915.  
15272862 A.P.Tampakaki, V.E.Fadouloglou, A.D.Gazi, N.J.Panopoulos, and M.Kokkinidis (2004).
Conserved features of type III secretion.
  Cell Microbiol, 6, 805-816.  
15341731 A.U.Singer, D.Desveaux, L.Betts, J.H.Chang, Z.Nimchuk, S.R.Grant, J.L.Dangl, and J.Sondek (2004).
Crystal structures of the type III effector protein AvrPphF and its chaperone reveal residues required for plant pathogenesis.
  Structure, 12, 1669-1681.
PDB codes: 1s21 1s28
15093830 H.Remaut, and G.Waksman (2004).
Structural biology of bacterial pathogenesis.
  Curr Opin Struct Biol, 14, 161-170.  
15073367 P.Cossart, and P.J.Sansonetti (2004).
Bacterial invasion: the paradigms of enteroinvasive pathogens.
  Science, 304, 242-248.  
15590783 P.Ghosh (2004).
Process of protein transport by the type III secretion system.
  Microbiol Mol Biol Rev, 68, 771-795.  
15577926 R.Dvorsky, and M.R.Ahmadian (2004).
Always look on the bright site of Rho: structural implications for a conserved intermolecular interface.
  EMBO Rep, 5, 1130-1136.  
15522075 R.J.Cain, R.D.Hayward, and V.Koronakis (2004).
The target cell plasma membrane is a critical interface for Salmonella cell entry effector-host interplay.
  Mol Microbiol, 54, 887-904.  
14756788 S.H.Lee, and J.E.Galán (2004).
Salmonella type III secretion-associated chaperones confer secretion-pathway specificity.
  Mol Microbiol, 51, 483-495.  
14640693 A.W.Maresso, M.J.Riese, and J.T.Barbieri (2003).
Molecular heterogeneity of a type III cytotoxin, Pseudomonas aeruginosa exoenzyme S.
  Biochemistry, 42, 14249-14257.  
14506477 C.E.Stebbins, and J.E.Galán (2003).
Priming virulence factors for delivery into the host.
  Nat Rev Mol Cell Biol, 4, 738-743.  
12742167 P.Boquet, and E.Lemichez (2003).
Bacterial virulence factors targeting Rho GTPases: parasitism or symbiosis?
  Trends Cell Biol, 13, 238-246.  
14636560 T.Kubori, and J.E.Galán (2003).
Temporal regulation of salmonella virulence effector function by proteasome-dependent protein degradation.
  Cell, 115, 333-342.  
11790850 A.G.Evdokimov, J.E.Tropea, K.M.Routzahn, and D.S.Waugh (2002).
Crystal structure of the Yersinia pestis GTPase activator YopE.
  Protein Sci, 11, 401-408.
PDB code: 1hy5
12093730 G.Buchwald, A.Friebel, J.E.Galán, W.D.Hardt, A.Wittinghofer, and K.Scheffzek (2002).
Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.
  EMBO J, 21, 3286-3295.
PDB code: 1gzs
12453223 K.J.Pederson, R.Krall, M.J.Riese, and J.T.Barbieri (2002).
Intracellular localization modulates targeting of ExoS, a type III cytotoxin, to eukaryotic signalling proteins.
  Mol Microbiol, 46, 1381-1390.  
12360287 M.R.Terebiznik, O.V.Vieira, S.L.Marcus, A.Slade, C.M.Yip, W.S.Trimble, T.Meyer, B.B.Finlay, and S.Grinstein (2002).
Elimination of host cell PtdIns(4,5)P(2) by bacterial SigD promotes membrane fission during invasion by Salmonella.
  Nat Cell Biol, 4, 766-773.  
12069791 R.A.Kahn, H.Fu, and C.R.Roy (2002).
Cellular hijacking: a common strategy for microbial infection.
  Trends Biochem Sci, 27, 308-314.  
12180912 R.M.Delahay, and G.Frankel (2002).
Coiled-coil proteins associated with type III secretion systems: a versatile domain revisited.
  Mol Microbiol, 45, 905-916.  
11423652 B.J.Staskawicz, M.B.Mudgett, J.L.Dangl, and J.E.Galan (2001).
Common and contrasting themes of plant and animal diseases.
  Science, 292, 2285-2289.  
11701921 I.R.Vetter, and A.Wittinghofer (2001).
The guanine nucleotide-binding switch in three dimensions.
  Science, 294, 1299-1304.  
11687484 J.E.Galán (2001).
Salmonella interactions with host cells: type III secretion at work.
  Annu Rev Cell Dev Biol, 17, 53-86.  
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.