DB code: D00510

RLCP classification 1.13.30100.19 : Hydrolysis
CATH domain 2.10.109.10 : Umud Fragment, subunit A Catalytic domain
1.10.10.10 : Arc Repressor Mutant, subunit A
E.C. 3.4.21.88
CSA 1jhf
M-CSA 1jhf
MACiE

CATH domain Related DB codes (homologues)
1.10.10.10 : Arc Repressor Mutant, subunit A D00452 D00077 D00517 T00055 T00113

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P0A7C2 LexA repressor
EC 3.4.21.88
NP_418467.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_492186.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
S24.001 (Serine)
PF01726 (LexA_DNA_bind)
PF00717 (Peptidase_S24)
[Graphical View]

KEGG enzyme name
repressor LexA
LexA repressor

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0A7C2 LEXA_ECOLI Hydrolysis of Ala-|-Gly bond in repressor lexA. Homodimer.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C99999 C00001 C00017 C00012 I00087 I00085 I00086
E.C.
Compound Repressor LexA H2O Protein Peptide Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein H2O peptide/protein
ChEBI 15377
PubChem 962
 22247451
1jhcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1jheA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ALA_84-GLY_85 (chain A) Unbound Unbound
1jheB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ALA_84-GLY_85 (chain B) Unbound Unbound
1jhfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1jhfB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1jhhA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1jhhB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:ALA_84-GLY_85 (chain B) Unbound Unbound
1jhfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1jhhA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1leaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1lebA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [4], [8], [13], [28]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1jhcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;LYS 156 MET 118; mutant S119A
1jheA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 119; MET 118;SER 119 mutant L89P, Q92W, E152A, K156A
1jheB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 119; MET 118;SER 119 mutant L89P, Q92W, E152A, K156A
1jhfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 119;LYS 156 MET 118;SER 119 mutant G85D
1jhfB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 119;LYS 156 MET 118;SER 119
1jhhA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;LYS 156 MET 118; mutant S119A
1jhhB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;LYS 156 MET 118; mutant S119A
1jhfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jhhA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1leaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1lebA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
Fig.4, p.3990-3991
[8]
Fig.1, p.12834-12835
[10]
Fig.2, p.416-417
[13]
p.921-922
[28]
p.588-589

References
[1]
Resource
Comments FUNCTION.
Medline ID 82037807
PubMed ID 7027256
Journal Proc Natl Acad Sci U S A
Year 1981
Volume 78
Pages 4204-8
Authors Brent R, Ptashne M
Title Mechanism of action of the lexA gene product.
Related PDB
Related UniProtKB P0A7C2
[2]
Resource
Comments FUNCTION.
Medline ID 82037806
PubMed ID 7027255
Journal Proc Natl Acad Sci U S A
Year 1981
Volume 78
Pages 4199-203
Authors Little JW, Mount DW, Yanisch-Perron CR
Title Purified lexA protein is a repressor of the recA and lexA genes.
Related PDB
Related UniProtKB P0A7C2
[3]
Resource
Comments
Medline ID
PubMed ID 3709524
Journal EMBO J
Year 1986
Volume 5
Pages 793-8
Authors Hurstel S, Granger-Schnarr M, Daune M, Schnarr M
Title In vitro binding of LexA repressor to DNA: evidence for the involvement of the amino-terminal domain.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3108885
Journal Proc Natl Acad Sci U S A
Year 1987
Volume 84
Pages 3987-91
Authors Slilaty SN, Little JW
Title Lysine-156 and serine-119 are required for LexA repressor cleavage: a possible mechanism.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2834329
Journal J Bacteriol
Year 1988
Volume 170
Pages 2163-73
Authors Lin LL, Little JW
Title Isolation and characterization of noncleavable (Ind-) mutants of the LexA repressor of Escherichia coli K-12.
Related PDB
Related UniProtKB
[6]
Resource
Comments STRUCTURE BY NMR.
Medline ID 89386639
PubMed ID 2780544
Journal Proc Natl Acad Sci U S A
Year 1989
Volume 86
Pages 6863-7
Authors Lamerichs RM, Padilla A, Boelens R, Kaptein R, Ottleben G, Ruterjans H, Granger-Schnarr M, Oertel P, Schnarr M
Title The amino-terminal domain of LexA repressor is alpha-helical but differs from canonical helix-turn-helix proteins: a two-dimensional 1H NMR study.
Related PDB
Related UniProtKB P0A7C2
[7]
Resource
Comments
Medline ID
PubMed ID 2184894
Journal Biochemistry
Year 1990
Volume 29
Pages 1961-70
Authors Hurstel S, Granger-Schnarr M, Schnarr M
Title The LexA repressor and its isolated amino-terminal domain interact cooperatively with poly[d(A-T)], a contiguous pseudo-operator, but not with random DNA: a circular dichroism study.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 2198279
Journal J Biol Chem
Year 1990
Volume 265
Pages 12828-35
Authors Roland KL, Little JW
Title Reaction of LexA repressor with diisopropyl fluorophosphate. A test of the serine protease model.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 2259342
Journal Mol Gen Genet
Year 1990
Volume 223
Pages 40-8
Authors Oertel-Buchheit P, Lamerichs RM, Schnarr M, Granger-Schnarr M
Title Genetic analysis of the LexA repressor: isolation and characterization of LexA(Def) mutant proteins.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 1911941
Journal Biochimie
Year 1991
Volume 73
Pages 411-21
Authors Little JW
Title Mechanism of specific LexA cleavage: autodigestion and the role of RecA coprotease.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 1911942
Journal Biochimie
Year 1991
Volume 73
Pages 423-31
Authors Schnarr M, Oertel-Buchheit P, Kazmaier M, Granger-Schnarr M
Title DNA binding properties of the LexA repressor.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 1815638
Journal J Biomol Struct Dyn
Year 1991
Volume 9
Pages 447-61
Authors Ottleben G, Messori L, Ruterjans H, Kaptein R, Granger-Schnarr M, Schnarr M
Title 1H-NMR investigation of the interaction of the amino terminal domain of the LexA repressor with a synthetic half-operator.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 1667880
Journal Protein Eng
Year 1991
Volume 4
Pages 919-22
Authors Slilaty SN, Vu HK
Title The role of electrostatic interactions in the mechanism of peptide bond hydrolysis by a Ser-Lys catalytic dyad.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 1602473
Journal J Mol Biol
Year 1992
Volume 225
Pages 609-20
Authors Oertel-Buchheit P, Porte D, Schnarr M, Granger-Schnarr M
Title Isolation and characterization of LexA mutant repressors with enhanced DNA binding affinity.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 1453451
Journal J Mol Biol
Year 1992
Volume 228
Pages 395-408
Authors Roland KL, Smith MH, Rupley JA, Little JW
Title In vitro analysis of mutant LexA proteins with an increased rate of specific cleavage.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 1620111
Journal Mol Cell Biol
Year 1992
Volume 12
Pages 3006-14
Authors Golemis EA, Brent R
Title Fused protein domains inhibit DNA binding by LexA.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 8513500
Journal Cell
Year 1993
Volume 73
Pages 1165-73
Authors Kim B, Little JW
Title LexA and lambda Cl repressors as enzymes: specific cleavage in an intermolecular reaction.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 8349538
Journal J Bacteriol
Year 1993
Volume 175
Pages 4943-50
Authors Little JW
Title LexA cleavage and other self-processing reactions.
Related PDB
Related UniProtKB
[19]
Resource
Comments STRUCTURE BY NMR.
Medline ID 94357165
PubMed ID 8076591
Journal EMBO J
Year 1994
Volume 13
Pages 3936-44
Authors Fogh RH, Ottleben G, Ruterjans H, Schnarr M, Boelens R, Kaptein R
Title Solution structure of the LexA repressor DNA binding domain determined by 1H NMR spectroscopy.
Related PDB 1lea 1leb
Related UniProtKB P0A7C2
[20]
Resource
Comments
Medline ID
PubMed ID 7716155
Journal Protein Eng
Year 1994
Volume 7
Pages 1449-53
Authors Holm L, Sander C, Ruterjans H, Schnarr M, Fogh R, Boelens R, Kaptein R
Title LexA repressor and iron uptake regulator from Escherichia coli: new members of the CAP-like DNA binding domain superfamily.
Related PDB
Related UniProtKB
[21]
Resource
Comments 3D-STRUCTURE MODELING.
Medline ID 95303877
PubMed ID 7784426
Journal Proteins
Year 1995
Volume 21
Pages 226-36
Authors Knegtel RM, Fogh RH, Ottleben G, Ruterjans H, Dumoulin P, Schnarr M, Boelens R, Kaptein R
Title A model for the LexA repressor DNA complex.
Related PDB
Related UniProtKB P0A7C2
[22]
Resource
Comments
Medline ID
PubMed ID 8605176
Journal Biochemistry
Year 1996
Volume 35
Pages 4279-86
Authors Dumoulin P, Ebright RH, Knegtel R, Kaptein R, Granger-Schnarr M, Schnarr M
Title Structure of the LexA repressor-DNA complex probed by affinity cleavage and affinity photo-cross-linking.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 8876169
Journal Proc Natl Acad Sci U S A
Year 1996
Volume 93
Pages 11528-33
Authors Shepley DP, Little JW
Title Mutant LexA proteins with specific defects in autodigestion.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 9512712
Journal J Mol Biol
Year 1998
Volume 276
Pages 405-15
Authors Konola JT, Guzzo A, Gow JB, Walker GC, Knight KL
Title Differential cleavage of LexA and UmuD mediated by recA Pro67 mutants: implications for common LexA and UmuD binding sites on RecA.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 9521130
Journal Protein Sci
Year 1998
Volume 7
Pages 512-5
Authors Oertel-Buchheit P, Reinbolt J, John M, Granger-Schnarr M, Schnarr M
Title A LexA mutant repressor with a relaxed inter-domain linker.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10692372
Journal J Bacteriol
Year 2000
Volume 182
Pages 1659-70
Authors Mustard JA, Little JW
Title Analysis of Escherichia coli RecA interactions with LexA, lambda CI, and UmuD by site-directed mutagenesis of recA.
Related PDB
Related UniProtKB
[27]
Resource
Comments Model
Medline ID
PubMed ID 11089640
Journal J Biomol Struct Dyn
Year 2000
Volume 18
Pages 181-97
Authors Chattopadhyaya R, Ghosh K, Namboodiri VM
Title Model of a LexA repressor dimer bound to recA operator.
Related PDB 1qaa
Related UniProtKB
[28]
Resource
Comments X-RAY DIFFRACTION
Medline ID
PubMed ID 11551506
Journal Cell
Year 2001
Volume 106
Pages 585-94
Authors Luo Y, Pfuetzner RA, Mosimann S, Paetzel M, Frey EA, Cherney M, Kim B, Little JW, Strynadka NC
Title Crystal structure of LexA: a conformational switch for regulation of self-cleavage.
Related PDB 1jhc 1jhe 1jhf 1jhh
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 11583611
Journal Mol Cell
Year 2001
Volume 8
Pages 486-7
Authors Walker GC
Title To cleave or not to cleave? Insights from the LexA crystal structure.
Related PDB
Related UniProtKB
[30]
Resource
Comments Model
Medline ID
PubMed ID 14769061
Journal J Biomol Struct Dyn
Year 2004
Volume 21
Pages 681-9
Authors Chattopadhyaya R, Pal A
Title Improved model of a LexA repressor dimer bound to recA operator.
Related PDB 1mvd
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 15929009
Journal J Biomol NMR
Year 2005
Volume 31
Pages 371-2
Authors Okon M, Pfuetzner RA, Vuckovic M, Little JW, Strynadka NC, McIntosh LP
Title Backbone chemical shift assignments of the LexA catalytic domain in its active conformation.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-S24.
This enzyme performs auto-catalysis (or auto-hydrolysis).
According to the literature [4], [10], [13] & [28], this enzyme catalyzes the following reaction:
(1) Lys156 acts as a general base to deprotonate the nucleophile, Ser119.
(2) Ser119 makes a nucleophilic attack on the carbonyl carbon atom of the target peptide bond (Ala84-Gly85), leading to a tetrahedral transition state.
(3) The negative charge of the tetrahedral transition state is stabilized by the oxyanion hole, composed of mainchain amide groups of Met118/Ser119.
(4) Lys156 acts as a general acid to protonate the leaving amino group, forming an intermediate.
(5) Lys156 probably acts as a general base to deprotonate and activate a water molecule.
(6) The activated water makes a nucleophilic attack on the carbonyl carbon of the intermediate.
(7) Lys156 acts as a general acid to protonate Ser119, completing the reaction.

Created Updated
2003-08-22 2011-02-21