2azm

X-ray diffraction
2.41Å resolution

Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX

Released:

Function and Biology Details

Reactions catalysed:
Succinyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-succinyldihydrolipoyl)lysine
ATP + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly = diphosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP
ATP + H(2)O + 4 H(+)(Side 1) = ADP + phosphate + 4 H(+)(Side 2)
(S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + NAD(P)(+) + H(2)O = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + NAD(P)H
(1a) an (RNA) containing cytidine = an (RNA)-3'-cytidine-2',3'-cyclophosphate + a 5'-hydroxy-ribonucleotide-3'-(RNA)
dUTP + H(2)O = dUMP + diphosphate
5-phospho-beta-D-ribosylamine + diphosphate + L-glutamate = L-glutamine + 5-phospho-alpha-D-ribose 1-diphosphate + H(2)O
1-(5-phospho-beta-D-ribosyl)-ATP + diphosphate = ATP + 5-phospho-alpha-D-ribose 1-diphosphate
4-amino-5-aminomethyl-2-methylpyrimidine + H(2)O = 4-amino-5-hydroxymethyl-2-methylpyrimidine + ammonia
ATP + a protein = ADP + a phosphoprotein
Quercetin + O(2) = 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H(+)
(1a) ATP + (R)-lipoate = lipoyl-AMP + diphosphate
ATP-dependent breakage, passage and rejoining of double-stranded DNA
(R)-propane-1,2-diol + NAD(+) = (R)-lactaldehyde + NADH
Malonyl-CoA + an [acyl-carrier-protein] = CoA + a malonyl-[acyl-carrier-protein]
2 alpha,alpha'-trehalose 6-mycolate = alpha,alpha'-trehalose + alpha,alpha'-trehalose 6,6'-bismycolate
Release of N-terminal proline from a peptide.
1-deoxy-D-xylulose 5-phosphate + 2-iminoacetate + thiocarboxy-[sulfur-carrier protein ThiS] = 2-((2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate + [sulfur-carrier protein ThiS] + 2 H(2)O
[Molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP + [cysteine desulfurase]-S-sulfanyl-L-cysteine + reduced acceptor = AMP + [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH(2)-C(O)SH + [cysteine desulfurase] + oxidized acceptor
7,8-dihydroneopterin = 7,8-dihydromonapterin
ATP + H(2)O + cellular protein(Side 1) = ADP + phosphate + cellular protein(Side 2)
Isochorismate + H(2)O = (2S,3S)-2,3-dihydroxy-2,3-dihydrobenzoate + pyruvate
A phosphate monoester + H(2)O = an alcohol + phosphate
Cleavage of peptide bonds with very broad specificity.
An aldehyde + NAD(P)(+) + H(2)O = a carboxylate + NAD(P)H
Diphosphate + H(2)O = 2 phosphate
4 Fe(2+) + 4 H(+) + O(2) = 4 Fe(3+) + 2 H(2)O
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid
N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA
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).
(1a) L-cysteine + [enzyme]-cysteine = L-alanine + [enzyme]-S-sulfanylcysteine
Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.
Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein]
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.
4-phosphonooxy-L-threonine + 2-oxoglutarate = (3R)-3-hydroxy-2-oxo-4-phosphonooxybutanoate + L-glutamate
7,8-dihydroneopterin 3'-triphosphate + H(2)O = 6-carboxy-5,6,7,8-tetrahydropterin + acetaldehyde + triphosphate
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
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
dCTP + 2 H(2)O = dUMP + diphosphate + NH(3)
ATP + shikimate = ADP + shikimate 3-phosphate
Tuberculosinyl diphosphate + adenosine = 1-tuberculosinyladenosine + diphosphate
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
Hydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose and cellotetraose, releasing cellobiose from the non-reducing ends of the chains
(S)-dihydroorotate + fumarate = orotate + succinate
An acyl-[acyl-carrier protein] + NAD(+) = a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH
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.
NTP + H(2)O = NDP + phosphate
A 5'-phosphopolynucleotide + H(2)O = a polynucleotide + phosphate
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine
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
1-deoxy-L-glycero-tetrulose 4-phosphate + 5-amino-6-(D-ribitylamino)uracil = 6,7-dimethyl-8-(D-ribityl)lumazine + 2 H(2)O + phosphate
2 3-phospho-D-glycerate + 2 H(+) = D-ribulose 1,5-bisphosphate + CO(2) + H(2)O
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
2 superoxide + 2 H(+) = O(2) + H(2)O(2)
RX + glutathione = HX + R-S-glutathione
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
D-xylopyranose = D-xylulose
(R)-lactate + NAD(+) = pyruvate + NADH
(R)-mandelonitrile = cyanide + benzaldehyde
Formate + NAD(+) = CO(2) + NADH
Random hydrolysis of (1->4)-beta-D-mannosidic linkages in mannans, galactomannans and glucomannans
ATP + pantetheine 4'-phosphate = diphosphate + 3'-dephospho-CoA
Hydrolysis of terminal, non-reducing beta-D-mannose residues in beta-D-mannosides
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'.
ATP + dTMP = ADP + dTDP
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-.
Cutin + H(2)O = cutin monomers
Peptidylproline (omega=180) = peptidylproline (omega=0)
5-methyltetrahydrofolate + NAD(P)(+) = 5,10-methylenetetrahydrofolate + NAD(P)H
S-adenosyl-L-methionine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-[mRNA]
[a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate
Endohydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans
L-histidinol phosphate + H(2)O = L-histidinol + phosphate
D-fructose 1,6-bisphosphate + H(2)O = D-fructose 6-phosphate + phosphate
L-aspartate 4-semialdehyde + phosphate + NADP(+) = L-4-aspartyl phosphate + NADPH
N-carbamoylputrescine + H(2)O = putrescine + CO(2) + NH(3)
H(2)CO(3) = CO(2) + H(2)O
L-quinate + NAD(P)(+) = 3-dehydroquinate + NAD(P)H
RH + Cl(-) + H(2)O(2) = RCl + 2 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.
Endonucleolytic cleavage to 5'-phosphomonoester.
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.
ATP + thymidine = ADP + thymidine 5'-phosphate
A 4-O-methyl-D-glucopyranuronate ester + H(2)O = 4-O-methyl-D-glucuronic acid + an alcohol
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).
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Acyl-CoA + 1,2-diacylglycerol = CoA + triacylglycerol
Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|- and the P1' position is occupied by Gly-|-
ATP + AMP = 2 ADP
L-alanine + H(2)O + NAD(+) = pyruvate + NH(3) + NADH
ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate
ATP + 6-hydroxymethyl-7,8-dihydropterin = AMP + 6-hydroxymethyl-7,8-dihydropterin diphosphate
2'-deoxycytidine + H(2)O = 2'-deoxyuridine + NH(3)
ATP + protoporphyrin IX + Mg(2+) + H(2)O = ADP + phosphate + Mg-protoporphyrin IX + 2 H(+)
L-glutamine + D-fructose 6-phosphate = L-glutamate + D-glucosamine 6-phosphate
Alpha-D-glucosamine 6-phosphate + H(2)O = D-fructose 6-phosphate + NH(3)
ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-tRNA(Pro)
ATP + (R)-pantothenate = ADP + (R)-4'-phosphopantothenate
7,8-dihydroneopterin + O(2) = 7,8-dihydroxanthopterin + formate + glycolaldehyde
Naphthalene + NADH + O(2) = (1R,2S)-1,2-dihydronaphthalene-1,2-diol + NAD(+)
N(2)-acetyl-L-ornithine + L-glutamate = L-ornithine + N-acetyl-L-glutamate
Selective cleavage of Tyr-|-Gly bond in picornavirus polyprotein.
NAD(P)H + O(2) = NAD(P)(+) + H(2)O(2)
7,8-dihydroneopterin = 6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
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.
A phosphatidylcholine + H(2)O = 1,2-diacyl-sn-glycerol + phosphocholine
(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H(2)O
UDP-alpha-D-glucose = UDP-alpha-D-galactose
ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide
Hydrolysis of terminal non-reducing beta-D-galactose residues in beta-D-galactosides
ATP + RNA(n) = diphosphate + RNA(n+1)
ATP + L-methionine + H(2)O = phosphate + diphosphate + S-adenosyl-L-methionine
ATP + H(2)O = ADP + phosphate
ADP-D-ribose 1''-phosphate + H(2)O = ADP-D-ribose + phosphate
Beta-D-ribopyranose = beta-D-ribofuranose
ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate
Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
3 ATP = pppA2'p5'A2'p5'A + 2 diphosphate
Hydrolysis of proteins in presence of ATP.
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
(1a) [acetyl-CoA C-acyltransferase]-S-acyl-L-cyteine + acetyl-CoA = 3-oxoacyl-CoA + [acetyl-CoA C-acyltransferase]-L-cyteine
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-hex-4-ulose + H(2)O
3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholanate + NAD(+) = 3-alpha,12-alpha-dihydroxy-7-oxo-5-beta-cholanate + NADH
Acyl-CoA + H(2)O = CoA + a carboxylate
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin
L-lysine + NADPH + O(2) = N(6)-hydroxy-L-lysine + NADP(+) + H(2)O
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
4 benzenediol + O(2) = 4 benzosemiquinone + 2 H(2)O
2-lysophosphatidylcholine + H(2)O = glycerophosphocholine + a carboxylate
A phenyl acetate + H(2)O = a phenol + acetate
NH(3) + 2 H(2)O + 6 ferricytochrome c = nitrite + 6 ferrocytochrome c + 7 H(+)
A 5'-ribonucleotide + H(2)O = a ribonucleoside + phosphate
N-acetyl-O-acetylneuraminate + H(2)O = N-acetylneuraminate + acetate
Reduced riboflavin + NAD(P)(+) = riboflavin + NAD(P)H
dTDP-4-dehydro-6-deoxy-alpha-D-glucose = dTDP-4-dehydro-beta-L-rhamnose
Oleoyl-[acyl-carrier-protein] + H(2)O = [acyl-carrier-protein] + oleate
ATP + L-glutamate + NH(3) = ADP + phosphate + L-glutamine
ATP + 2-(formamido)-N(1)-(5-phospho-D-ribosyl)acetamidine = ADP + phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole
ATP + succinate + CoA = ADP + phosphate + succinyl-CoA
A chalcone = a flavanone
D-glucarate = 5-dehydro-4-deoxy-D-glucarate + H(2)O
L-arginine + H(2)O = L-ornithine + urea
ATP = 3',5'-cyclic AMP + diphosphate
S-adenosyl 3-(methylthio)propylamine + putrescine = 5'-S-methyl-5'-thioadenosine + spermidine
NAD(+) + glycine + sulfide = nicotinamide + ADP-5-ethyl-4-methylthiazole-2-carboxylate + 3 H(2)O
All bonds known to be hydrolyzed by this endopeptidase have arginine in P1 and an acidic residue in P4. P6 is often occupied by an acidic residue or by a hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage.
2 bilirubin + O(2) = 2 biliverdin + 2 H(2)O
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = diphosphate + geranylgeranyl diphosphate
Acetyl-CoA + phosphate = CoA + acetyl phosphate
Geranylgeranyl diphosphate = (+)-copalyl diphosphate
L-arginine + 2-oxoglutarate + O(2) = (3S)-3-hydroxy-L-arginine + succinate + CO(2)
DNA (containing 4-O-methylthymine) + protein L-cysteine = DNA (without 4-O-methylthymine) + protein S-methyl-L-cysteine
Hydrolysis of terminal non-reducing alpha-L-arabinofuranoside residues in alpha-L-arabinosides
ATP + glycerol = ADP + sn-glycerol 3-phosphate
H(2) + A = AH(2)
An aldehyde + NAD(+) + H(2)O = a carboxylate + NADH
Palmitoyl-CoA + H(2)O = CoA + palmitate
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 (1->4)-linked alpha-D-glucose residues with release of alpha-D-glucose
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.
(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
N(1)-methylguanine(37) in tRNA(Phe) + pyruvate + S-adenosyl-L-methionine = 4-demethylwyosine(37) in tRNA(Phe) + L-methionine + 5'-deoxyadenosine + CO(2) + H(2)O
Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Mediator of DNA damage checkpoint protein 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 207 amino acids
Theoretical weight: 22.88 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: Q14676 (Residues: 1883-2089; Coverage: 10%)
Gene names: KIAA0170, MDC1, NFBD1
Structure domains: BRCT domain
Histone H2AX Chains: C, D
Molecule details ›
Chains: C, D
Length: 10 amino acids
Theoretical weight: 1.24 KDa
Source organism: Homo sapiens
Expression system: Not provided
UniProt:
  • Canonical: P16104 (Residues: 134-143; Coverage: 7%)
Gene names: H2AFX, H2AX

Ligands and Environments

No bound ligands
2 modified residues:

Experiments and Validation Details

Entry percentile scores
X-ray source: SRS BEAMLINE PX14.2
Spacegroup: P212121
Unit cell:
a: 67.437Å b: 75.609Å c: 114.849Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.194 0.191 0.248
Expression systems:
  • Escherichia coli BL21
  • Not provided