3rbn

X-ray diffraction
2.16Å resolution

Crystal structure of MutL protein homolog 1 isoform 1 [Homo sapiens]

Released:
Source organism: Homo sapiens
Entry authors: Dong A, Dombrovsky L, Wernimont A, Loppnau P, Bountra C, Weigelt J, Arrowsmith CH, Edwards AM, Min J, Wu H, Structural Genomics Consortium (SGC)

Function and Biology Details

Reactions catalysed:
Hydrolysis of proteins in presence of ATP.
Phosphoenolpyruvate + D-erythrose 4-phosphate + H(2)O = 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate + phosphate
Release of an N-terminal dipeptide from a peptide comprising four or more residues, with broad specificity. Also acts on dipeptidyl 2-naphthylamides.
ATP + H(2)O + 4 H(+)(Side 1) = ADP + phosphate + 4 H(+)(Side 2)
Endohydrolysis of beta-(1->4)-linkages between D-glucosamine residues in a partly acetylated chitosan
dUTP + H(2)O = dUMP + diphosphate
Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
ATP + D-ribose = ADP + D-ribose 5-phosphate
L-rhamnonate = 2-dehydro-3-deoxy-L-rhamnonate + H(2)O
Succinate + a quinone = fumarate + a quinol
(S)-3-hydroxybutanoyl-CoA + NADP(+) = 3-acetoacetyl-CoA + NADPH
ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol hexakisphosphate
(S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
Acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-|-Val
L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate
Isochorismate + H(2)O = (2S,3S)-2,3-dihydroxy-2,3-dihydrobenzoate + pyruvate
A phosphate monoester + H(2)O = an alcohol + phosphate
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin
Cleavage of peptide bonds with very broad specificity.
Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
Diphosphate + H(2)O = 2 phosphate
L-lysine + NADPH + O(2) = N(6)-hydroxy-L-lysine + NADP(+) + H(2)O
4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid
The peptide bond hydrolyzed can be designated -C-|-A-A-X in which C is an S-isoprenylated cysteine residue, A is usually aliphatic and X is the C-terminal residue of the substrate protein, and may be any of several amino acids.
4 benzenediol + O(2) = 4 benzosemiquinone + 2 H(2)O
N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA
(1a) L-tyrosine + 1/2 O(2) = L-dopa
L-asparagine + H(2)O = L-aspartate + NH(3)
(1a) L-cysteine + [enzyme]-cysteine = L-alanine + [enzyme]-S-sulfanylcysteine
Urea + H(2)O = CO(2) + 2 NH(3)
Triacylglycerol + H(2)O = diacylglycerol + a carboxylate
A carboxylic ester + H(2)O = an alcohol + a carboxylate
L-alanine = D-alanine
Hydrolysis of (1->4)-beta-D-xylans, to remove successive D-xylose residues from the non-reducing termini
(2S)-2-hydroxy-3,4-dioxopentyl phosphate = 3-hydroxy-2,4-dioxopentyl phosphate
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.
CoA-(4'-phosphopantetheine) + apo-[acyl-carrier-protein] = adenosine 3',5'-bisphosphate + holo-[acyl-carrier-protein]
Random endo-hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and chitodextrins
Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins
Thioredoxin + ROOH = thioredoxin disulfide + H(2)O + ROH
Nitric oxide + H(2)O + ferricytochrome c = nitrite + ferrocytochrome c + 2 H(+)
NH(3) + 2 H(2)O + 6 ferricytochrome c = nitrite + 6 ferrocytochrome c + 7 H(+)
Sucrose + ((1->6)-alpha-D-glucosyl)(n) = D-fructose + ((1->6)-alpha-D-glucosyl)(n+1)
Thioredoxin + NADP(+) = thioredoxin disulfide + NADPH
Protein dithiol + NAD(P)(+) = protein disulfide + NAD(P)H
Formyl-L-methionyl peptide + H(2)O = formate + methionyl peptide
ATP + H(2)O + cellular protein(Side 1) = ADP + phosphate + cellular protein(Side 2)
L-erythro-3,5-diaminohexanoate + H(2)O + NAD(+) = (S)-5-amino-3-oxohexanoate + NH(3) + NADH
Pyruvate + L-aspartate-4-semialdehyde = (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate + H(2)O
NTP + H(2)O = NDP + phosphate
An aliphatic amide = a nitrile + H(2)O
Cellobiose = 4-O-beta-D-glucopyranosyl-D-mannose
dTDP-4-dehydro-6-deoxy-alpha-D-glucose = dTDP-4-dehydro-beta-L-rhamnose
Oxalyl-CoA = formyl-CoA + CO(2)
L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate
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.
S-adenosyl-L-methionine + guanine(37) in tRNA = S-adenosyl-L-homocysteine + N(1)-methylguanine(37) in tRNA
ATP + L-glutamate + NH(3) = ADP + phosphate + L-glutamine
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine
ATP + succinate + CoA = ADP + phosphate + succinyl-CoA
(1a) L-glutamine + H(2)O = L-glutamate + NH(3)
dTTP + alpha-D-glucose 1-phosphate = diphosphate + dTDP-alpha-D-glucose
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.
(3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP(+) = 3-oxoacyl-[acyl-carrier-protein] + NADPH
Isocitrate = succinate + glyoxylate
ATP + (R)-5-diphosphomevalonate = ADP + phosphate + isopentenyl diphosphate + CO(2)
A beta-lactam + H(2)O = a substituted beta-amino acid
ATP + D-ribose 5-phosphate = AMP + 5-phospho-alpha-D-ribose 1-diphosphate
N-((R)-4'-phosphopantothenoyl)-L-cysteine = pantotheine 4'-phosphate + CO(2)
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
2 reduced ferredoxin + NADP(+) + H(+) = 2 oxidized ferredoxin + NADPH
RX + glutathione = HX + R-S-glutathione
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
L-tyrosine + 2-oxoglutarate = 4-hydroxyphenylpyruvate + L-glutamate
S-adenosyl 3-(methylthio)propylamine + putrescine = 5'-S-methyl-5'-thioadenosine + spermidine
6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate
ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide
UTP + alpha-D-glucose 1-phosphate = diphosphate + UDP-glucose
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.
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
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'.
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-.
CTP + sn-glycerol 3-phosphate = diphosphate + CDP-glycerol
Maltose = alpha,alpha-trehalose
(1a) [acetyl-CoA C-acyltransferase]-S-acyl-L-cyteine + acetyl-CoA = 3-oxoacyl-CoA + [acetyl-CoA C-acyltransferase]-L-cyteine
(1a) L-cystathionine = L-cysteine + 2-aminobut-2-enoate
2 H(2)O(2) = O(2) + 2 H(2)O
Peptidylproline (omega=180) = peptidylproline (omega=0)
2 bilirubin + O(2) = 2 biliverdin + 2 H(2)O
Endohydrolysis of (1->4)-beta-D-xylosidic linkages in xylans
(R)-3-hydroxybutanoate + NAD(+) = acetoacetate + NADH
Endohydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans
Endohydrolysis of (1->4)-alpha-D-glucosidic linkages in polysaccharides containing three or more (1->4)-alpha-linked D-glucose units
(R)-3-hydroxyacyl-CoA + NADP(+) = 3-oxoacyl-CoA + NADPH
D-galactonate = 2-dehydro-3-deoxy-D-galactonate + H(2)O
Hydrolysis of terminal non-reducing alpha-L-rhamnose residues in alpha-L-rhamnosides
N-carbamoylputrescine + H(2)O = putrescine + CO(2) + NH(3)
N,N-dimethylformamide + H(2)O = dimethylamine + formate
H(2)CO(3) = CO(2) + H(2)O
Eliminative cleavage of alginate to give oligosaccharides with 4-deoxy-alpha-L-erythro-hex-4-enuronosyl groups at their non-reducing ends and beta-D-mannuronate at their reducing end.
S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha-D-ribose 1-phosphate
Methylamine + H(2)O + 2 oxidized [amicyanin] = formaldehyde + NH(3) + 2 reduced [amicyanin]
A glutathione-S-conjugate + H(2)O = an (L-cysteinylglycine)-S-conjugate + L-glutamate
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).
ATP + acetate + CoA = ADP + phosphate + acetyl-CoA
Inosine 5'-phosphate + NAD(+) + H(2)O = xanthosine 5'-phosphate + NADH
Chorismate = isochorismate
Hydrolyzes single-stranded DNA or mismatched double-stranded DNA and polynucleotides, releasing free uracil
Anthranilate + N,N-dimethyl-1,4-phenylenediamine + 2 NAD(+) = 2-(4-dimethylaminophenyl)diazenylbenzoate + 2 NADH
Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
L-arginine + 2-oxoglutarate + O(2) = (3S)-3-hydroxy-L-arginine + succinate + CO(2)
H(2) + NAD(+) = H(+) + NADH
Reduced plastocyanin + oxidized ferredoxin + light = oxidized plastocyanin + reduced ferredoxin
UDP-glucose + 2 NAD(+) + H(2)O = UDP-glucuronate + 2 NADH
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
ATP + AMP = 2 ADP
An alpha-L-fucoside + H(2)O = L-fucose + an alcohol
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine(4) = S-adenosyl-L-homocysteine + a [histone H3]-N(6)-methyl-L-lysine(4)
Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides
ATP + thiamine = AMP + thiamine diphosphate
NAD(P)H + a quinone = NAD(P)(+) + a hydroquinone
S-adenosyl-L-methionine + a 5'-(5'-triphosphoguanosine)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA]
A (3R)-3-hydroxyacyl-[acyl-carrier-protein] + a UDP-3-O-((3R)-hydroxyacyl)-alpha-D-glucosamine = a UDP-2-N,3-O-bis((3R)-3-hydroxyacyl)-alpha-D-glucosamine + a holo-[acyl-carrier-protein]
ATP + glycerol = ADP + sn-glycerol 3-phosphate
4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate
CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-((R)-4'-phosphopantothenoyl)-L-cysteine
4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O
H(2) + A = AH(2)
Pectin + n H(2)O = n methanol + pectate
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.
GTP + a 5'-diphospho-[mRNA] = diphosphate + a 5'-(5'-triphosphoguanosine)-[mRNA]
O-acetyl-L-serine + hydrogen sulfide = L-cysteine + acetate
3-dehydroquinate = 3-dehydroshikimate + H(2)O
2-phospho-D-glycerate = phosphoenolpyruvate + H(2)O
Tetradecanoyl-CoA + an N-terminal-glycyl-[protein] = CoA + an N-terminal-N-tetradecanoylglycyl-[protein]
ATP + L-leucine + tRNA(Leu) = AMP + diphosphate + L-leucyl-tRNA(Leu)
O(4)-succinyl-L-homoserine + L-cysteine = L-cystathionine + succinate
(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H(2)O
A purine nucleoside + H(2)O = D-ribose + a purine base
The primary cleavage site is at 67-His-|-Lys-68 in human C5a with a minor secondary cleavage site at 58-Ala-|-Ser-59
Alpha-D-glucosamine 6-phosphate + H(2)O = D-fructose 6-phosphate + NH(3)
Preferential cleavage: (Ac)(2)-L-Lys-D-Ala-|-D-Ala. Also transpeptidation of peptidyl-alanyl moieties that are N-acyl substituents of D-alanine.
ATP + L-pyrrolysine + tRNA(Pyl) = AMP + diphosphate + L-pyrrolysyl-tRNA(Pyl)
Hydrolysis of terminal, non-reducing beta-D-glucosyl residues with release of beta-D-glucose
Hydrolysis of terminal non-reducing beta-D-galactose residues in beta-D-galactosides
ATP + L-phenylalanine + tRNA(Phe) = AMP + diphosphate + L-phenylalanyl-tRNA(Phe)
ATP + H(2)O = ADP + phosphate
TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
L-ornithine = L-proline + NH(3)
Quinol + 2 ferricytochrome c(Side 2) = quinone + 2 ferrocytochrome c(Side 2) + 2 H(+)(Side 2)
2 superoxide + 2 H(+) = O(2) + H(2)O(2)
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
D-ribulose 5-phosphate = D-xylulose 5-phosphate
A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid
Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.
Biochemical function:
Biological process:
Cellular component:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
DNA mismatch repair protein Mlh1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 284 amino acids
Theoretical weight: 33.03 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P40692 (Residues: 486-751; Coverage: 35%)
Gene names: COCA2, MLH1

Ligands and Environments

No bound ligands
1 modified residue:

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 19-ID
Spacegroup: P212121
Unit cell:
a: 63.505Å b: 64.7Å c: 130.932Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.209 0.208 0.251
Expression system: Escherichia coli BL21(DE3)