1x2j

X-ray diffraction
1.6Å resolution

Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2

Released:

Function and Biology Details

Reactions catalysed:
Phosphoenolpyruvate + D-erythrose 4-phosphate + H(2)O = 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate + phosphate
Hydrolysis of terminal, non-reducing branched (1->3)-alpha-D-galactosidic residues, producing free D-galactose
dUTP + H(2)O = dUMP + diphosphate
Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
Carbamoyl phosphate + L-ornithine = phosphate + L-citrulline
ATP + a protein = ADP + a phosphoprotein
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-hex-4-ulose + H(2)O
(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
(2Z,4E)-2-hydroxyhexa-2,4-dienedioate = (3E)-2-oxohex-3-enedioate
Release of N-terminal proline from a peptide.
Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolyzed, but rates on arylamides are exceedingly low.
(1a) (2R,3S)-3-isopropylmalate = 2-isopropylmaleate + H(2)O
1-haloalkane + H(2)O = a primary alcohol + halide
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin
Cleavage of peptide bonds with very broad specificity.
ATP-dependent cleavage of peptide bonds with broad specificity.
Diphosphate + H(2)O = 2 phosphate
(1a) 2 Fe(2+) + O(2) + 4 H(2)O = 2 (FeO(OH)) + 4 H(+) + H(2)O(2)
4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid
4 benzenediol + O(2) = 4 benzosemiquinone + 2 H(2)O
Chorismate = prephenate
L-asparagine + H(2)O = L-aspartate + NH(3)
Urea + H(2)O = CO(2) + 2 NH(3)
Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein]
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine
Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
2 glutathione + ROOH = glutathione disulfide + H(2)O + ROH
Cyclo(L-tyrosyl-L-tyrosyl) + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H(+) + O(2) = mycocyclosin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H(2)O
Nitric oxide + H(2)O + ferricytochrome c = nitrite + ferrocytochrome c + 2 H(+)
Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|- and the P1' position is occupied by Gly-|-
[Amino group carrier protein]-C-terminal-gamma-(L-lysyl)-L-glutamate + H(2)O = [amino group carrier protein]-C-terminal-L-glutamate + L-lysine
A [lipoyl-carrier protein]-N(6)-((R)-dihydrolipoyl)-L-lysine + ROOH = a [lipoyl-carrier protein]-N(6)-((R)-lipoyl)-L-lysine + H(2)O + ROH
dTDP-beta-L-rhamnose + NADP(+) = dTDP-4-dehydro-beta-L-rhamnose + NADPH
An acyl-[acyl-carrier protein] + NAD(+) = a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH
Isochorismate = salicylate + pyruvate
NTP + H(2)O = NDP + phosphate
ATP + H(2)O + 4 H(+)(Side 1) = ADP + phosphate + 4 H(+)(Side 2)
S-adenosyl-L-methionine + adenine(58) in tRNA = S-adenosyl-L-homocysteine + N(1)-methyladenine(58) in tRNA
5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole = 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate
6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO(2) + NADPH
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine
ATP + deamido-NAD(+) + L-glutamine + H(2)O = AMP + diphosphate + NAD(+) + L-glutamate
(1a) ATP + [DNA ligase]-L-lysine = [DNA ligase]-N(6)-(5'-adenylyl)-L-lysine + diphosphate
5,10-methylenetetrahydrofolate + dUMP + NADPH = dTMP + tetrahydrofolate + NADP(+)
Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.
A beta-lactam + H(2)O = a substituted beta-amino acid
RX + glutathione = HX + R-S-glutathione
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
L-tryptophan + O(2) = N-formyl-L-kynurenine
ATP = 3',5'-cyclic AMP + diphosphate
6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate
Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec; and Leu-Tyr-Leu-|-Tyr-Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also occurs).
Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.
Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
Hydrolyzes glutaminyl bonds, and activity is further restricted by preferences for the amino acids in P6 - P1' that vary with the species of potyvirus, e.g. Glu-Xaa-Xaa-Tyr-Xaa-Gln-|-(Ser or Gly) for the enzyme from tobacco etch virus. The natural substrate is the viral polyprotein, but other proteins and oligopeptides containing the appropriate consensus sequence are also cleaved.
Hydrolyzes a Gly-|-Gly bond at its own C-terminus, commonly in the sequence -Tyr-Xaa-Val-Gly-|-Gly, in the processing of the potyviral polyprotein.
Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-|-Arg- and -Lys-|-Arg-.
L-lysine + 2-oxoglutarate = (S)-2-amino-6-oxohexanoate + L-glutamate
ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate
Peptidylproline (omega=180) = peptidylproline (omega=0)
Choline = trimethylamine + acetaldehyde
2 bilirubin + O(2) = 2 biliverdin + 2 H(2)O
An aldehyde + H(2)O + 2 oxidized ferredoxin = a carboxylate + 2 H(+) + 2 reduced ferredoxin
Endohydrolysis of (1->4)-beta-D-xylosidic linkages in xylans
Release of a C-terminal amino acid with broad specificity, except for -Pro.
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = diphosphate + geranylgeranyl diphosphate
N-carbamoylputrescine + H(2)O = putrescine + CO(2) + NH(3)
(S)-malate = fumarate + H(2)O
H(2)CO(3) = CO(2) + H(2)O
N(6)-(Delta(2)-isopentenyl)-adenosine 5'-phosphate + H(2)O = N(6)-(dimethylallyl)adenine + D-ribose 5'-phosphate
ADP-alpha-D-glucose + D-glucose 6-phosphate = ADP + alpha,alpha-trehalose 6-phosphate
ATP + thymidine = ADP + thymidine 5'-phosphate
Geranylgeranyl diphosphate = (+)-copalyl diphosphate
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH
Chorismate = isochorismate
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
S-adenosyl-L-methionine + uracil(1498) in 16S rRNA = S-adenosyl-L-homocysteine + N(3)-methyluracil(1498) in 16S rRNA 
L-arginine + 2-oxoglutarate + O(2) = (3S)-3-hydroxy-L-arginine + succinate + CO(2)
ATP + dTMP = ADP + dTDP
Succinyl-CoA + (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + H(2)O = CoA + N-succinyl-L-2-amino-6-oxoheptanedioate
Acetyl-CoA + a 2-deoxystreptamine antibiotic = CoA + N(3)-acetyl-2-deoxystreptamine antibiotic
L-glutamate + H(2)O + NADP(+) = 2-oxoglutarate + NH(3) + NADPH
ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
ATP + 6-hydroxymethyl-7,8-dihydropterin = AMP + 6-hydroxymethyl-7,8-dihydropterin diphosphate
ATP + (R)-pantothenate = ADP + (R)-4'-phosphopantothenate
(S)-dihydroorotate + a quinone = orotate + a quinol
(1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate = 2-succinylbenzoate + H(2)O
Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
Selective cleavage of Tyr-|-Gly bond in picornavirus polyprotein.
(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H(2)O
Beta-D-ribopyranose = beta-D-ribofuranose
AMP + H(2)O = D-ribose 5-phosphate + adenine
ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide
Preferential cleavage: (Ac)(2)-L-Lys-D-Ala-|-D-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine.
Hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactolipids
Hydrolysis of terminal non-reducing beta-D-galactose residues in beta-D-galactosides
ATP + H(2)O = ADP + phosphate
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
2-C-methyl-D-erythritol 4-phosphate + NADP(+) = 1-deoxy-D-xylulose 5-phosphate + NADPH
Hydrolysis of (1->6)-alpha-D-glucosidic linkages in pullulan, amylopectin and glycogen, and in the alpha- and beta-limit dextrins of amylopectin and glycogen.
The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate
L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine = 2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine
L-glutaminyl-peptide = 5-oxoprolyl-peptide + NH(3)
ATP + L-aspartate = ADP + 4-phospho-L-aspartate
Biochemical function:
Biological process:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Kelch-like ECH-associated protein 1 Chain: A
Molecule details ›
Chain: A
Length: 316 amino acids
Theoretical weight: 34.71 KDa
Source organism: Mus musculus
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Z2X8 (Residues: 309-624; Coverage: 51%)
Gene names: Inrf2, Keap1, Kiaa0132
Sequence domains: Kelch motif
Structure domains: Kelch-type beta propeller

Ligands and Environments

1 bound ligand:
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SPRING-8 BEAMLINE BL26B2
Spacegroup: P61
Unit cell:
a: 103.062Å b: 103.062Å c: 54.947Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.173 0.168 0.2
Expression system: Escherichia coli