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PDBsum entry 1jhf

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
1jhf
Jmol
Contents
Protein chains
197 a.a. *
111 a.a. *
Ligands
SO4
Waters ×162
* Residue conservation analysis
PDB id:
1jhf
Name: Hydrolase
Title: Lexa g85d mutant
Structure: Lexa repressor. Chain: a, b. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: lexa. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.240     R-free:   0.263
Authors: Y.Luo,R.A.Pfuetzner,S.Mosimann,J.W.Little,N.C.J.Strynadka
Key ref:
Y.Luo et al. (2001). Crystal structure of LexA: a conformational switch for regulation of self-cleavage. Cell, 106, 585-594. PubMed id: 11551506 DOI: 10.1016/S0092-8674(01)00479-2
Date:
27-Jun-01     Release date:   19-Sep-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0A7C2  (LEXA_ECOLI) -  LexA repressor
Seq:
Struc:
202 a.a.
197 a.a.*
Protein chain
Pfam   ArchSchema ?
P0A7C2  (LEXA_ECOLI) -  LexA repressor
Seq:
Struc:
202 a.a.
111 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.3.4.21.88  - Repressor LexA.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of Ala-|-Gly bond in repressor lexA.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to DNA damage stimulus   8 terms 
  Biochemical function     hydrolase activity     3 terms  

 

 
DOI no: 10.1016/S0092-8674(01)00479-2 Cell 106:585-594 (2001)
PubMed id: 11551506  
 
 
Crystal structure of LexA: a conformational switch for regulation of self-cleavage.
Y.Luo, R.A.Pfuetzner, S.Mosimann, M.Paetzel, E.A.Frey, M.Cherney, B.Kim, J.W.Little, N.C.Strynadka.
 
  ABSTRACT  
 
LexA repressor undergoes a self-cleavage reaction. In vivo, this reaction requires an activated form of RecA, but it occurs spontaneously in vitro at high pH. Accordingly, LexA must both allow self-cleavage and yet prevent this reaction in the absence of a stimulus. We have solved the crystal structures of several mutant forms of LexA. Strikingly, two distinct conformations are observed, one compatible with cleavage, and the other in which the cleavage site is approximately 20 A from the catalytic center. Our analysis provides insight into the structural and energetic features that modulate the interconversion between these two forms and hence the rate of the self-cleavage reaction. We suggest RecA activates the self-cleavage of LexA and related proteins through selective stabilization of the cleavable conformation.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Mapping of Previously Characterized MutantsA stereo ribbon representation of LexA (C form) with LexA Ind^− mutations (in blue), Ind^s mutations (in green), and λ cI RecA-specific mutations (in brown) mapped on the structure (as based on Figure 1)
Figure 6.
Figure 6. The Exposed Hydrophobic Surface of LexAThe catalytic core of LexA is shown in a molecular surface representation with the hydrophobic area highlighted in green (GRASP; Honig and Nicholls, 1995). The CSR and linker loop are shown as red and purple ribbons, respectively. The side chains of selected hydrophobic side chains on the CSR that become differentially exposed to solvent are highlighted in a cyan ball and stick representation.(A) NC form.(B) C form
 
  The above figures are reprinted by permission from Cell Press: Cell (2001, 106, 585-594) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21295583 C.L.Brooks, C.Lazareno-Saez, J.S.Lamoureux, M.W.Mak, and M.J.Lemieux (2011).
Insights into substrate gating in H. influenzae rhomboid.
  J Mol Biol, 407, 687-697.
PDB code: 3odj
21295698 F.Capotosti, S.Guernier, F.Lammers, P.Waridel, Y.Cai, J.Jin, J.W.Conaway, R.C.Conaway, and W.Herr (2011).
O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1.
  Cell, 144, 376-388.  
21521654 P.Bhaumik, Y.Horimoto, H.Xiao, T.Miura, K.Hidaka, Y.Kiso, A.Wlodawer, R.Y.Yada, and A.Gustchina (2011).
Crystal structures of the free and inhibited forms of plasmepsin I (PMI) from Plasmodium falciparum.
  J Struct Biol, 175, 73-84.
PDB codes: 3qrv 3qs1
21212055 T.D.Thi, E.López, A.Rodríguez-Rojas, J.Rodríguez-Beltrán, A.Couce, J.R.Guelfo, A.Castañeda-García, and J.Blázquez (2011).
Effect of recA inactivation on mutagenesis of Escherichia coli exposed to sublethal concentrations of antimicrobials.
  J Antimicrob Chemother, 66, 531-538.  
20703307 A.P.Zhang, Y.Z.Pigli, and P.A.Rice (2010).
Structure of the LexA-DNA complex and implications for SOS box measurement.
  Nature, 466, 883-886.
PDB codes: 3jso 3jsp 3k3r
20410074 E.León, G.Navarro-Avilés, C.M.Santiveri, C.Flores-Flores, M.Rico, C.González, F.J.Murillo, M.Elías-Arnanz, M.A.Jiménez, and S.Padmanabhan (2010).
A bacterial antirepressor with SH3 domain topology mimics operator DNA in sequestering the repressor DNA recognition helix.
  Nucleic Acids Res, 38, 5226-5241.
PDB code: 2kss
20030588 I.Weinheimer, K.Boonrod, M.Moser, M.Zwiebel, M.Füllgrabe, G.Krczal, and M.Wassenegger (2010).
Analysis of an autoproteolytic activity of rice yellow mottle virus silencing suppressor P1.
  Biol Chem, 391, 271-281.  
20457791 L.Medina-Ruiz, S.Campoy, C.Latasa, P.Cardenas, J.C.Alonso, and J.Barbé (2010).
Overexpression of the recA gene decreases oral but not intraperitoneal fitness of Salmonella enterica.
  Infect Immun, 78, 3217-3225.  
19540941 M.D.Sutton (2010).
Coordinating DNA polymerase traffic during high and low fidelity synthesis.
  Biochim Biophys Acta, 1804, 1167-1179.  
19487441 E.López, and J.Blázquez (2009).
Effect of subinhibitory concentrations of antibiotics on intrachromosomal homologous recombination in Escherichia coli.
  Antimicrob Agents Chemother, 53, 3411-3415.  
19942138 K.Barreto, V.M.Bharathikumar, A.Ricardo, J.F.DeCoteau, Y.Luo, and C.R.Geyer (2009).
A genetic screen for isolating "lariat" Peptide inhibitors of protein function.
  Chem Biol, 16, 1148-1157.  
19633075 P.J.Beuning, S.Chan, L.S.Waters, H.Addepalli, J.N.Ollivierre, and G.C.Walker (2009).
Characterization of novel alleles of the Escherichia coli umuDC genes identifies additional interaction sites of UmuC with the beta clamp.
  J Bacteriol, 191, 5910-5920.  
19250317 T.Ganguly, M.Das, A.Bandhu, P.K.Chanda, B.Jana, R.Mondal, and S.Sau (2009).
Physicochemical properties and distinct DNA binding capacity of the repressor of temperate Staphylococcus aureus phage phi11.
  FEBS J, 276, 1975-1985.  
19013467 V.E.Galkin, X.Yu, J.Bielnicki, D.Ndjonka, C.E.Bell, and E.H.Egelman (2009).
Cleavage of bacteriophage lambda cI repressor involves the RecA C-terminal domain.
  J Mol Biol, 385, 779-787.  
18234215 K.C.Giese, C.B.Michalowski, and J.W.Little (2008).
RecA-dependent cleavage of LexA dimers.
  J Mol Biol, 377, 148-161.  
18824507 O.D.Ekici, M.Paetzel, and R.E.Dalbey (2008).
Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration.
  Protein Sci, 17, 2023-2037.  
18432246 S.Stayrook, P.Jaru-Ampornpan, J.Ni, A.Hochschild, and M.Lewis (2008).
Crystal structure of the lambda repressor and a model for pairwise cooperative operator binding.
  Nature, 452, 1022-1025.
PDB code: 3bdn
17962420 A.C.Babić, and J.W.Little (2007).
Cooperative DNA binding by CI repressor is dispensable in a phage lambda variant.
  Proc Natl Acad Sci U S A, 104, 17741-17746.  
17639348 D.Ferreira, E.Leitão, J.Sjöholm, P.Oliveira, P.Lindblad, P.Moradas-Ferreira, and P.Tamagnini (2007).
Transcription and regulation of the hydrogenase(s) accessory genes, hypFCDEAB, in the cyanobacterium Lyngbya majuscula CCAP 1446/4.
  Arch Microbiol, 188, 609-617.  
17376074 E.López, M.Elez, I.Matic, and J.Blázquez (2007).
Antibiotic-mediated recombination: ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli.
  Mol Microbiol, 64, 83-93.  
17233828 G.Navarro-Avilés, M.A.Jiménez, M.C.Pérez-Marín, C.González, M.Rico, F.J.Murillo, M.Elías-Arnanz, and S.Padmanabhan (2007).
Structural basis for operator and antirepressor recognition by Myxococcus xanthus CarA repressor.
  Mol Microbiol, 63, 980-994.
PDB code: 2jml
17434938 M.Ni, S.Y.Wang, J.K.Li, and Q.Ouyang (2007).
Simulating the temporal modulation of inducible DNA damage response in Escherichia coli.
  Biophys J, 93, 62-73.  
17088354 S.A.Coleman, E.R.Fischer, D.C.Cockrell, D.E.Voth, D.Howe, D.J.Mead, J.E.Samuel, and R.A.Heinzen (2007).
Proteome and antigen profiling of Coxiella burnetii developmental forms.
  Infect Immun, 75, 290-298.  
16934834 D.Ndjonka, and C.E.Bell (2006).
Structure of a hyper-cleavable monomeric fragment of phage lambda repressor containing the cleavage site region.
  J Mol Biol, 362, 479-489.
PDB codes: 2hnf 2ho0
16607265 H.D.Ulrich (2006).
Deubiquitinating PCNA: a downside to DNA damage tolerance.
  Nat Cell Biol, 8, 303-305.  
  16582483 J.Lee, A.R.Feldman, B.Delmas, and M.Paetzel (2006).
Expression, purification and crystallization of a birnavirus-encoded protease, VP4, from blotched snakehead virus (BSNV).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 353-356.  
  17142905 J.Lee, A.R.Feldman, E.Chiu, C.Chan, Y.N.Kim, B.Delmas, and M.Paetzel (2006).
Purification, crystallization and preliminary X-ray analysis of truncated and mutant forms of VP4 protease from infectious pancreatic necrosis virus.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1235-1238.  
16541078 J.W.Lee, and J.D.Helmann (2006).
The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation.
  Nature, 440, 363-367.  
16464848 P.J.Beuning, S.M.Simon, A.Zemla, D.Barsky, and G.C.Walker (2006).
A non-cleavable UmuD variant that acts as a UmuD' mimic.
  J Biol Chem, 281, 9633-9640.  
16484219 R.Matsumi, H.Atomi, and T.Imanaka (2006).
Identification of the amino acid residues essential for proteolytic activity in an archaeal signal peptide peptidase.
  J Biol Chem, 281, 10533-10539.  
16877706 T.V.Rotanova, I.Botos, E.E.Melnikov, F.Rasulova, A.Gustchina, M.R.Maurizi, and A.Wlodawer (2006).
Slicing a protease: structural features of the ATP-dependent Lon proteases gleaned from investigations of isolated domains.
  Protein Sci, 15, 1815-1828.  
16077107 B.C.McCabe, D.R.Pawlowski, and G.B.Koudelka (2005).
The bacteriophage 434 repressor dimer preferentially undergoes autoproteolysis by an intramolecular mechanism.
  J Bacteriol, 187, 5624-5630.  
16269821 E.S.Groban, M.B.Johnson, P.Banky, P.G.Burnett, G.L.Calderon, E.C.Dwyer, S.N.Fuller, B.Gebre, L.M.King, I.N.Sheren, L.D.Von Mutius, T.M.O'Gara, and C.M.Lovett (2005).
Binding of the Bacillus subtilis LexA protein to the SOS operator.
  Nucleic Acids Res, 33, 6287-6295.  
15797197 I.B.Dodd, K.E.Shearwin, and J.B.Egan (2005).
Revisited gene regulation in bacteriophage lambda.
  Curr Opin Genet Dev, 15, 145-152.  
16077133 J.Cuñé, P.Cullen, G.Mazon, S.Campoy, B.Adler, and J.Barbe (2005).
The Leptospira interrogans lexA gene is not autoregulated.
  J Bacteriol, 187, 5841-5845.  
15929009 M.Okon, R.A.Pfuetzner, M.Vuckovic, J.W.Little, N.C.Strynadka, and L.P.McIntosh (2005).
Backbone chemical shift assignments of the LexA catalytic domain in its active conformation.
  J Biomol NMR, 31, 371-372.  
15664197 M.Quinones, H.H.Kimsey, and M.K.Waldor (2005).
LexA cleavage is required for CTX prophage induction.
  Mol Cell, 17, 291-300.  
16030231 S.Campoy, N.Salvador, P.Cortés, I.Erill, and J.Barbé (2005).
Expression of canonical SOS genes is not under LexA repression in Bdellovibrio bacteriovorus.
  J Bacteriol, 187, 5367-5375.  
15516580 A.P.Koudelka, L.A.Hufnagel, and G.B.Koudelka (2004).
Purification and characterization of the repressor of the shiga toxin-encoding bacteriophage 933W: DNA binding, gene regulation, and autocleavage.
  J Bacteriol, 186, 7659-7669.  
14679217 D.R.Pawlowski, and G.B.Koudelka (2004).
The preferred substrate for RecA-mediated cleavage of bacteriophage 434 repressor is the DNA-bound dimer.
  J Bacteriol, 186, 1-7.  
14665623 I.Botos, E.E.Melnikov, S.Cherry, J.E.Tropea, A.G.Khalatova, F.Rasulova, Z.Dauter, M.R.Maurizi, T.V.Rotanova, A.Wlodawer, and A.Gustchina (2004).
The catalytic domain of Escherichia coli Lon protease has a unique fold and a Ser-Lys dyad in the active site.
  J Biol Chem, 279, 8140-8148.
PDB codes: 1rr9 1rre
15604457 I.Erill, M.Jara, N.Salvador, M.Escribano, S.Campoy, and J.Barbé (2004).
Differences in LexA regulon structure among Proteobacteria through in vivo assisted comparative genomics.
  Nucleic Acids Res, 32, 6617-6626.  
15458417 M.Abella, I.Erill, M.Jara, G.Mazón, S.Campoy, and J.Barbé (2004).
Widespread distribution of a lexA-regulated DNA damage-inducible multiple gene cassette in the Proteobacteria phylum.
  Mol Microbiol, 54, 212-222.  
12867456 A.R.Fernández de Henestrosa, J.Cuñé, G.Mazón, B.L.Dubbels, D.A.Bazylinski, and J.Barbé (2003).
Characterization of a new LexA binding motif in the marine magnetotactic bacterium strain MC-1.
  J Bacteriol, 185, 4471-4482.  
12667450 J.M.Flynn, S.B.Neher, Y.I.Kim, R.T.Sauer, and T.A.Baker (2003).
Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals.
  Mol Cell, 11, 671-683.  
14527288 L.H.Caporale (2003).
Natural selection and the emergence of a mutation phenotype: an update of the evolutionary synthesis considering mechanisms that affect genome variation.
  Annu Rev Microbiol, 57, 467-485.  
12670973 M.Jara, C.Núñez, S.Campoy, A.R.Fernández de Henestrosa, D.R.Lovley, and J.Barbé (2003).
Geobacter sulfurreducens has two autoregulated lexA genes whose products do not bind the recA promoter: differing responses of lexA and recA to DNA damage.
  J Bacteriol, 185, 2493-2502.  
12730132 S.B.Neher, J.M.Flynn, R.T.Sauer, and T.A.Baker (2003).
Latent ClpX-recognition signals ensure LexA destruction after DNA damage.
  Genes Dev, 17, 1084-1089.  
12864858 S.Campoy, M.Fontes, S.Padmanabhan, P.Cortés, M.Llagostera, and J.Barbé (2003).
LexA-independent DNA damage-mediated induction of gene expression in Myxococcus xanthus.
  Mol Microbiol, 49, 769-781.  
14612247 T.Jansèn, H.Kidron, A.Soitamo, T.Salminen, and P.Mäenpää (2003).
Transcriptional regulation and structural modelling of the Synechocystis sp. PCC 6803 carboxyl-terminal endoprotease family.
  FEMS Microbiol Lett, 228, 121-128.  
12374844 A.R.Fernández de Henestrosa, J.Cuñé, I.Erill, J.K.Magnuson, and J.Barbé (2002).
A green nonsulfur bacterium, Dehalococcoides ethenogenes, with the LexA binding sequence found in gram-positive organisms.
  J Bacteriol, 184, 6073-6080.  
11917014 A.Tapias, S.Fernández, J.C.Alonso, and J.Barbé (2002).
Rhodobacter sphaeroides LexA has dual activity: optimising and repressing recA gene transcription.
  Nucleic Acids Res, 30, 1539-1546.  
12393890 A.V.Kajava, S.N.Zolov, K.I.Pyatkov, A.E.Kalinin, and M.A.Nesmeyanova (2002).
Processing of Escherichia coli alkaline phosphatase. Sequence requirements and possible conformations of the -6 to -4 region of the signal peptide.
  J Biol Chem, 277, 50396-50402.  
11856856 S.Shin, T.H.Lee, H.M.Koo, S.Y.Kim, H.S.Lee, Y.S.Kim, and B.H.Oh (2002).
Crystallization and preliminary X-ray crystallographic analysis of malonamidase E2, an amidase signature family member.
  Acta Crystallogr D Biol Crystallogr, 58, 562-563.  
12032064 S.Shin, T.H.Lee, N.C.Ha, H.M.Koo, S.Y.Kim, H.S.Lee, Y.S.Kim, and B.H.Oh (2002).
Structure of malonamidase E2 reveals a novel Ser-cisSer-Lys catalytic triad in a new serine hydrolase fold that is prevalent in nature.
  EMBO J, 21, 2509-2516.
PDB codes: 1ock 1ocl 1ocm
11583611 G.C.Walker (2001).
To cleave or not to cleave? Insights from the LexA crystal structure.
  Mol Cell, 8, 486-487.  
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.