4ed1

X-ray diffraction
1.81Å resolution

Human DNA polymerase eta - DNA ternary complex: AT crystal at pH 7.0 (Na+ MES) with 1 Ca2+ ion

Released:
Source organism: Homo sapiens
Primary publication:
Watching DNA polymerase η make a phosphodiester bond.
Nature 487 196-201 (2012)
PMID: 22785315

Function and Biology Details

Reactions catalysed:
Hydrolysis of terminal, non-reducing branched (1->3)-alpha-D-galactosidic residues, producing free D-galactose
ATP + H(2)O + 4 H(+)(Side 1) = ADP + phosphate + 4 H(+)(Side 2)
4 sulfur + 4 H(2)O + O(2) = 2 H(2)S + 2 HSO(3)(-) + 2 H(+)
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
dUTP + H(2)O = dUMP + diphosphate
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
Uridine + phosphate = uracil + alpha-D-ribose 1-phosphate 
(8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate = cyclic pyranopterin phosphate + diphosphate
Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate
ATP + a protein = ADP + a phosphoprotein
(1a) glutaryl-CoA + electron-transfer flavoprotein = (E)-glutaconyl-CoA + reduced electron-transfer flavoprotein
(1a) 2 L-ascorbate + H(2)O(2) + 2 H(+) = 2 monodehydroascorbate + 2 H(2)O
(1a) [acetyl-CoA C-acyltransferase]-S-acyl-L-cyteine + acetyl-CoA = 3-oxoacyl-CoA + [acetyl-CoA C-acyltransferase]-L-cyteine
(9Z)-(13S)-12,13-epoxyoctadeca-9,11,15-trienoate = (15Z)-12-oxophyto-10,15-dienoate
(S)-3-hydroxybutanoyl-CoA + NADP(+) = 3-acetoacetyl-CoA + NADPH
D-glucose + O(2) = 2-dehydro-D-glucose + H(2)O(2)
Endonucleolytic cleavage to 5'-phosphomonoester.
6-phospho-D-glucono-1,5-lactone + H(2)O = 6-phospho-D-gluconate
ATP-dependent breakage, passage and rejoining of double-stranded DNA
Geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2E,6E)-farnesyl diphosphate
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.
ATP + L-methionine + H(2)O = phosphate + diphosphate + S-adenosyl-L-methionine
Prenyl diphosphate + isopentenyl diphosphate = diphosphate + geranyl diphosphate
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + succinate
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin
Formate + NAD(+) = CO(2) + NADH
Farnesyl diphosphate + protein-cysteine = S-farnesyl protein + diphosphate
D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate
An acylphosphate + H(2)O = a carboxylate + 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
UDP-alpha-D-galactopyranose = UDP-alpha-D-galactofuranose
4 benzenediol + O(2) = 4 benzosemiquinone + 2 H(2)O
N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA
L-asparagine + H(2)O = L-aspartate + NH(3)
Urea + H(2)O = CO(2) + 2 NH(3)
An acetic ester + H(2)O = an alcohol + acetate
L-serine + L-homocysteine = L-cystathionine + H(2)O
Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.
A carboxylic ester + H(2)O = an alcohol + a carboxylate
Propane-1,2-diol = propanal + H(2)O
Random hydrolysis of (1->4)-beta-D-mannosidic linkages in mannans, galactomannans and glucomannans
(1a) NADP(+) = 2'-phospho-cyclic ADP-ribose + nicotinamide
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
4-phosphonooxy-L-threonine + 2-oxoglutarate = (3R)-3-hydroxy-2-oxo-4-phosphonooxybutanoate + L-glutamate
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.
Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|- and the P1' position is occupied by Gly-|-
CTP + phosphocholine = diphosphate + CDP-choline
Orotidine 5'-phosphate = UMP + CO(2)
N-acetyl-O-acetylneuraminate + H(2)O = N-acetylneuraminate + acetate
Tetradecanoyl-CoA + an N-terminal-glycyl-[protein] = CoA + an N-terminal-N-tetradecanoylglycyl-[protein]
An acyl-[acyl-carrier protein] + NAD(+) = a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH
ATP + an [amino-group carrier protein]-C-terminal-N-(1,4-dicarboxybutan-1-yl)-L-glutamine = ADP + an [amino-group carrier protein]-C-terminal-N-(1-carboxy-5-phosphooxy-5-oxopentan-1-yl)-L-glutamine
The primary cleavage site is at 67-His-|-Lys-68 in human C5a with a minor secondary cleavage site at 58-Ala-|-Ser-59
4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate
NTP + H(2)O = NDP + phosphate
H(2) + 2 ferricytochrome c3 = 2 H(+) + 2 ferrocytochrome c3
A (3R)-3-hydroxyacyl-[acyl-carrier protein] = a trans-2-enoyl-[acyl-carrier protein] + H(2)O
5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole = 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate
L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate
ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
dTTP + alpha-D-glucose 1-phosphate = diphosphate + dTDP-alpha-D-glucose
L-threonine + NAD(+) = L-2-amino-3-oxobutanoate + NADH
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.
ATP + (R)-5-diphosphomevalonate = ADP + phosphate + isopentenyl diphosphate + CO(2)
A beta-lactam + H(2)O = a substituted beta-amino acid
Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate
Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
Transfers a segment of a (1->4)-alpha-D-glucan to a new position in an acceptor, which may be glucose or a (1->4)-alpha-D-glucan
RX + glutathione = HX + R-S-glutathione
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
L-arginine + H(2)O = L-ornithine + urea
D-glyceraldehyde 3-phosphate = glycerone phosphate
6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate
D-xylopyranose = D-xylulose
2-dehydro-3-deoxy-6-phosphate-D-gluconate = pyruvate + D-glyceraldehyde 3-phosphate
Cleaves -Ala-|-Ser- and -Ala-|-Ala- bonds in the scaffold protein.
(1a) L-methionine = methanethiol + 2-aminobut-2-enoate
2-phospho-D-glycerate = 3-phospho-D-glycerate
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)
ATP + sulfate = diphosphate + adenylyl sulfate
Hydrolysis of the bonds linking certain hydrophobic residues in hemoglobin or globin. Also cleaves small molecules substrates such as Ala-Leu-Glu-Arg-Thr-Phe-|-Phe(NO(2))-Ser-Phe-Pro-Thr.
3-phospho-D-glycerate + NAD(+) = 3-phosphonooxypyruvate + NADH
L-alanine = D-alanine
2 H(2)O(2) = O(2) + 2 H(2)O
2 phenolic donor + H(2)O(2) = 2 phenoxyl radical of the donor + 2 H(2)O
Peptidylproline (omega=180) = peptidylproline (omega=0)
CO + H(2)O + 2 oxidized ferredoxin = CO(2) + 2 reduced ferredoxin + 2 H(+)
(R)-3-hydroxybutanoate + NAD(+) = acetoacetate + NADH
3-hydroxy-2-methylpropanoate + NAD(+) = 2-methyl-3-oxopropanoate + NADH
Endohydrolysis of (1->3)- or (1->4)-linkages in beta-D-glucans when the glucose residue whose reducing group is involved in the linkage to be hydrolyzed is itself substituted at C-3.
ATP + (phosphate)(n) = ADP + (phosphate)(n+1)
L-aspartate 4-semialdehyde + phosphate + NADP(+) = L-4-aspartyl phosphate + NADPH
2 superoxide + 2 H(+) = O(2) + H(2)O(2)
S-adenosyl-L-methionine + 3,4-dihydroxy-trans-cinnamate = S-adenosyl-L-homocysteine + 3-methoxy-4-hydroxy-trans-cinnamate
D-glucosyl-N-acylsphingosine + H(2)O = D-glucose + N-acylsphingosine
Ethylnitronate + O(2) = acetaldehyde + nitrite + other products
Sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-ribose 5-phosphate + D-xylulose 5-phosphate
Exonucleolytic cleavage in the 3'- to 5'-direction to yield nucleoside 5'-phosphates
ATP + riboflavin = ADP + FMN
5,10-methylenetetrahydrofolate + dUMP + NADPH = dTMP + tetrahydrofolate + NADP(+)
Inosine 5'-phosphate + NAD(+) + H(2)O = xanthosine 5'-phosphate + NADH
Anthranilate + N,N-dimethyl-1,4-phenylenediamine + 2 NAD(+) = 2-(4-dimethylaminophenyl)diazenylbenzoate + 2 NADH
Hydrolysis of DNA containing ring-opened 7-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine
7-alpha,12-alpha-dihydroxy-3-oxochol-4-en-24-oyl-CoA = 12-alpha-hydroxy-3-oxochola-4,6-dien-24-oyl-CoA + H(2)O
A primary alcohol + 2 cytochrome c(L) = an aldehyde + 2 reduced cytochrome c(L) + 2 H(+)
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
ATP + deoxyguanosine = ADP + dGMP
SsDNA + n NTP = ssDNA/pppN(pN)(n-1) hybrid + (n-1) diphosphate
Hydrolysis of terminal non-reducing alpha-L-arabinofuranoside residues in alpha-L-arabinosides
2-methyl-3-oxopropanoate + CoA + H(2)O + NAD(+) = propanoyl-CoA + HCO(3)(-) + NADH
(2Z,4E)-2-hydroxyhexa-2,4-dienedioate = (3E)-2-oxohex-3-enedioate
S-adenosyl-L-methionine + (S)-scoulerine = S-adenosyl-L-homocysteine + (S)-tetrahydrocolumbamine
NAD(P)H + a quinone = NAD(P)(+) + a hydroquinone
Endohydrolysis of (1->4)-beta-D-xylosidic linkages in xylans
ATP + L-methionine + tRNA(Met) = AMP + diphosphate + L-methionyl-tRNA(Met)
ATP + thiamine = AMP + thiamine diphosphate
ATP + glycerol = ADP + sn-glycerol 3-phosphate
Formylmethanofuran + H(2)O + 2 oxidized ferredoxin [iron-sulfur] cluster = CO(2) + methanofuran + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H(+)
Endohydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans
(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.
An aliphatic amide = a nitrile + H(2)O
RCH(2)NHR' + H(2)O + O(2) = RCHO + R'NH(2) + H(2)O(2)
Pyruvate + L-aspartate-4-semialdehyde = (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate + H(2)O
D-fructose 6-phosphate + phosphate = acetyl phosphate + D-erythrose 4-phosphate + H(2)O
UDP-alpha-D-glucose = UDP-alpha-D-galactose
(1a) NAD(+) = cyclic ADP-ribose + nicotinamide
An alcohol + NADP(+) = an aldehyde + NADPH
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 beta-D-glucosyl residues with release of beta-D-glucose
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
L-proline + NAD(P)(+) = 1-pyrroline-5-carboxylate + NAD(P)H
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
Hydrolysis of terminal non-reducing alpha-L-rhamnose residues in alpha-L-rhamnosides
(GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n)-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol = (GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala))(n+1)-diphosphoundecaprenol + undecaprenyl diphosphate
L-ornithine = L-proline + NH(3)
Quinol + 2 ferricytochrome c(Side 2) = quinone + 2 ferrocytochrome c(Side 2) + 2 H(+)(Side 2)
4 ferrocytochrome c + O(2) + 4 H(+) = 4 ferricytochrome c + 2 H(2)O
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
ATP + (R)-5-phosphomevalonate = ADP + (R)-5-diphosphomevalonate
NADH + ubiquinone + 5 H(+)(Side 1) = NAD(+) + ubiquinol + 4 H(+)(Side 2)
4-fumarylacetoacetate + H(2)O = acetoacetate + fumarate
Biochemical function:
Biological process:
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
Entry contents:
1 distinct polypeptide molecule
2 distinct DNA molecules
Macromolecules (3 distinct):
DNA polymerase eta Chain: A
Molecule details ›
Chain: A
Length: 435 amino acids
Theoretical weight: 48.62 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Y253 (Residues: 1-432; Coverage: 61%)
Gene names: POLH, RAD30, RAD30A, XPV
Sequence domains: impB/mucB/samB family
Structure domains:
DNA (5'-D(*CP*AP*TP*TP*AP*TP*GP*AP*CP*GP*CP*T)-3') Chain: T
Molecule details ›
Chain: T
Length: 12 nucleotides
Theoretical weight: 3.64 KDa
Source organism: Homo sapiens
Expression system: Not provided
DNA (5'-D(*AP*GP*CP*GP*TP*CP*AP*T)-3') Chain: P
Molecule details ›
Chain: P
Length: 8 nucleotides
Theoretical weight: 2.43 KDa
Source organism: Homo sapiens
Expression system: Not provided

Ligands and Environments

No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 22-BM
Spacegroup: P61
Unit cell:
a: 98.786Å b: 98.786Å c: 82.431Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.172 0.17 0.207
Expression systems:
  • Escherichia coli
  • Not provided