1mr1

X-ray diffraction
2.85Å resolution

Crystal Structure of a Smad4-Ski Complex

Released:

Function and Biology Details

Reactions catalysed:
ATP + L-arginine = ADP + N(omega)-phospho-L-arginine
A phosphate monoester + H(2)O = an alcohol + phosphate
(1a) an (RNA) containing cytidine = an (RNA)-3'-cytidine-2',3'-cyclophosphate + a 5'-hydroxy-ribonucleotide-3'-(RNA)
Cleavage of peptide bonds with very broad specificity.
Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
Oxaloacetate = pyruvate + CO(2)
5-phospho-beta-D-ribosylamine + diphosphate + L-glutamate = L-glutamine + 5-phospho-alpha-D-ribose 1-diphosphate + H(2)O
ATP + a protein = ADP + a phosphoprotein
1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate = 1-C-(3-indolyl)-glycerol 3-phosphate + CO(2) + H(2)O
N-(5-phospho-D-ribosyl)-anthranilate + diphosphate = anthranilate + 5-phospho-alpha-D-ribose 1-diphosphate
2-(N(omega)-L-arginino)succinate = fumarate + L-arginine
ATP = 3',5'-cyclic AMP + diphosphate
Succinate + a quinone = fumarate + a quinol
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.
Isochorismate + H(2)O = (2S,3S)-2,3-dihydroxy-2,3-dihydrobenzoate + pyruvate
1-haloalkane + H(2)O = a primary alcohol + halide
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
Formate + NAD(+) = CO(2) + NADH
S-adenosyl-L-methionine + 8-amino-7-oxononanoate = S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
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
ATP + H(2)O + 4 H(+)(Side 1) = ADP + phosphate + 4 H(+)(Side 2)
N-substituted aminoacyl-tRNA + H(2)O = N-substituted amino acid + tRNA
Chorismate = prephenate
4-(2-carboxyphenyl)-4-oxobutanoyl-CoA = 1,4-dihydroxy-2-naphthoyl-CoA + H(2)O
Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein]
L-alanine = D-alanine
Random hydrolysis of (1->4)-beta-D-mannosidic linkages in mannans, galactomannans and glucomannans
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.
Acetyl-CoA + alpha-D-glucosamine 1-phosphate = CoA + N-acetyl-alpha-D-glucosamine 1-phosphate
Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1' positions. Cleaves 1-Phe-|-Val-2, 4-Gln-|-His-5, 13-Glu-|-Ala-14, 14-Ala-|-Leu-15, 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17, 23-Gly-|-Phe-24, 24-Phe-|-Phe-25 and 25-Phe-|-Tyr-26 bonds in the B chain of insulin.
Thioredoxin + ROOH = thioredoxin disulfide + H(2)O + ROH
ATP + shikimate = ADP + shikimate 3-phosphate
Tuberculosinyl diphosphate + adenosine = 1-tuberculosinyladenosine + diphosphate
Mycoredoxin + ROOH = mycoredoxin disulfide + H(2)O + ROH
N-acetyl-O-acetylneuraminate + H(2)O = N-acetylneuraminate + acetate
(S)-dihydroorotate + fumarate = orotate + succinate
An acyl-[acyl-carrier protein] + NAD(+) = a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH
2-hydroxy-4-oxobutane-1,2,4-tricarboxylate = oxaloacetate + pyruvate
Hydrolyzes poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
ATP + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate + meso-2,6-diaminoheptanedioate = ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminoheptanedioate
NTP + H(2)O = NDP + phosphate
A 5'-phosphopolynucleotide + H(2)O = a polynucleotide + phosphate
ATP + L-glutamate + NH(3) = ADP + phosphate + L-glutamine
Maltose = alpha,alpha-trehalose
UTP + N-acetyl-alpha-D-glucosamine 1-phosphate = diphosphate + UDP-N-acetyl-alpha-D-glucosamine
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.
1-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H(2)O = 1-alkyl-sn-glycero-3-phosphocholine + acetate
A beta-lactam + H(2)O = a substituted beta-amino acid
Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate
2 3-phospho-D-glycerate + 2 H(+) = D-ribulose 1,5-bisphosphate + CO(2) + H(2)O
dUTP + H(2)O = dUMP + diphosphate
RX + glutathione = HX + R-S-glutathione
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
D-glyceraldehyde 3-phosphate = glycerone phosphate
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.
Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO(2)
2 H(2)O(2) = O(2) + 2 H(2)O
ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate
Peptidylproline (omega=180) = peptidylproline (omega=0)
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
Acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
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)-alpha-D-glucosidic linkages in polysaccharides containing three or more (1->4)-alpha-linked D-glucose units
L-aspartate 4-semialdehyde + phosphate + NADP(+) = L-4-aspartyl phosphate + NADPH
2 superoxide + 2 H(+) = O(2) + H(2)O(2)
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.
ADP-alpha-D-glucose + D-glucose 6-phosphate = ADP + alpha,alpha-trehalose 6-phosphate
L-lysine = cadaverine + CO(2)
2-deoxy-D-ribose 5-phosphate = D-glyceraldehyde 3-phosphate + acetaldehyde
ATP + thymidine = ADP + thymidine 5'-phosphate
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)
Hydrolyzes single-stranded DNA or mismatched double-stranded DNA and polynucleotides, releasing free uracil
(R)-lactate + NAD(+) = pyruvate + NADH
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
An ultra-long-chain mono-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein] = an ultra-long-chain mono-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO(2) + a holo-[acyl-carrier protein]
Shikimate + NADP(+) = 3-dehydroshikimate + NADPH
L-alanine + H(2)O + NAD(+) = pyruvate + NH(3) + NADH
ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides
5-hydroxyisourate + H(2)O = 5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
ATP + (R)-pantothenate = ADP + (R)-4'-phosphopantothenate
ATP + L-glutamine + tRNA(Gln) = AMP + diphosphate + L-glutaminyl-tRNA(Gln)
tRNA(n+1) + phosphate = tRNA(n) + a nucleoside diphosphate
Naphthalene + NADH + O(2) = (1R,2S)-1,2-dihydronaphthalene-1,2-diol + NAD(+)
(1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate = 2-succinylbenzoate + H(2)O
N(2)-acetyl-L-ornithine + L-glutamate = L-ornithine + N-acetyl-L-glutamate
Selective cleavage of Tyr-|-Gly bond in picornavirus polyprotein.
An aldehyde + NAD(+) + H(2)O = a carboxylate + NADH
Acetyl-CoA + L-serine = CoA + O-acetyl-L-serine
S-adenosyl-L-methionine + guanosine(2251) in 23S rRNA = S-adenosyl-L-homocysteine + 2'-O-methylguanosine(2251) in 23S rRNA 
Selective cleavage of Arg-|-Lys bond in complement factor B when in complex with complement subcomponent C3b or with cobra venom factor.
Pyruvate + L-aspartate-4-semialdehyde = (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate + H(2)O
(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.
ATP + RNA(n) = diphosphate + RNA(n+1)
Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier-protein] + CoA + CO(2) 
ATP + H(2)O = ADP + phosphate
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
ADP-D-ribose 1''-phosphate + H(2)O = ADP-D-ribose + phosphate
(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
2-C-methyl-D-erythritol 4-phosphate + NADP(+) = 1-deoxy-D-xylulose 5-phosphate + NADPH
N-carbamoylputrescine + H(2)O = putrescine + CO(2) + NH(3)
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
CTP + 2-C-methyl-D-erythritol 4-phosphate = diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
2-iminobutanoate + H(2)O = 2-oxobutanoate + NH(3)
[Amino group carrier protein]-C-terminal-gamma-(L-lysyl)-L-glutamate + H(2)O = [amino group carrier protein]-C-terminal-L-glutamate + L-lysine
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin
[Protein]-N(pi)-phospho-L-histidine + lactose(Side 1) = [protein]-L-histidine + lactose 6'-phosphate(Side 2)
4 benzenediol + O(2) = 4 benzosemiquinone + 2 H(2)O
(1a) (2R,3S)-3-isopropylmalate = 2-isopropylmaleate + H(2)O
(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
ATP-dependent cleavage of peptide bonds with broad specificity.
Diphosphate + H(2)O = 2 phosphate
Cleaves -Ala-|-Ser- and -Ala-|-Ala- bonds in the scaffold protein.
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
L-cystathionine + H(2)O = L-homocysteine + NH(3) + pyruvate
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
2 glutathione + ROOH = glutathione disulfide + H(2)O + ROH
NADH + ROOH + H(+) = NAD(+) + H(2)O + ROH
Nitric oxide + H(2)O + ferricytochrome c = nitrite + ferrocytochrome c + 2 H(+)
ATP + H(2)O + cellular protein(Side 1) = ADP + phosphate + cellular protein(Side 2)
5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole = 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate
Malonyl-CoA + an [acyl-carrier-protein] = CoA + a malonyl-[acyl-carrier-protein]
L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate
(1a) ATP + [DNA ligase]-L-lysine = [DNA ligase]-N(6)-(5'-adenylyl)-L-lysine + diphosphate
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate = (S)-allantoin + CO(2)
D-glucarate = 5-dehydro-4-deoxy-D-glucarate + H(2)O
Hg + NADP(+) + H(+) = Hg(2+) + NADPH
L-arginine + 2-oxoglutarate + O(2) = (3S)-3-hydroxy-L-arginine + succinate + CO(2)
Cutin + H(2)O = cutin monomers
Maleate = fumarate
2 phenolic donor + H(2)O(2) = 2 phenoxyl radical of the donor + 2 H(2)O
Endohydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans
Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|- and the P1' position is occupied by Gly-|-
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.
Eliminative cleavage of (1->4)-alpha-D-galacturonan to give oligosaccharides with 4-deoxy-alpha-D-galact-4-enuronosyl groups at their non-reducing ends
Hydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose and similar substrates, releasing cellobiose from the reducing ends of the chains.
D-firefly luciferin + O(2) + ATP = firefly oxyluciferin + CO(2) + AMP + diphosphate + light
Acetyl-CoA + a 2-deoxystreptamine antibiotic = CoA + N(3)-acetyl-2-deoxystreptamine antibiotic
L-glutamate + H(2)O + NAD(+) = 2-oxoglutarate + NH(3) + NADH
L-glutamate + H(2)O + NADP(+) = 2-oxoglutarate + NH(3) + NADPH
ATP + thiamine = AMP + thiamine diphosphate
RH + [reduced NADPH--hemoprotein reductase] + O(2) = ROH + [oxidized NADPH--hemoprotein reductase] + H(2)O
Hydrolysis of terminal non-reducing alpha-L-arabinofuranoside residues in alpha-L-arabinosides
NAD(+) + protein-L-arginine = nicotinamide + N(omega)-(ADP-D-ribosyl)-protein-L-arginine
2 nitric oxide + 2 O(2) + NAD(P)H = 2 nitrate + NAD(P)(+) + H(+)
GDP-beta-L-fucose + NADP(+) = GDP-4-dehydro-alpha-D-rhamnose + NADPH
(1a) L-cystathionine = L-cysteine + 2-aminobut-2-enoate
[F-actin]-L-methionine + NADPH + O(2) + H(+) = [F-actin]-L-methionine-(R)-S-oxide + NADP(+) + H(2)O
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
Hydrolysis of terminal, non-reducing (1->4)-linked alpha-D-glucose residues with release of alpha-D-glucose
Hydrolysis of terminal, non-reducing beta-D-glucosyl residues with release of beta-D-glucose
Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.
ATP + N-acetyl-L-glutamate = ADP + N-acetyl-L-glutamate 5-phosphate
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Mothers against decapentaplegic homolog 4 Chains: A, B
Molecule details ›
Chains: A, B
Length: 235 amino acids
Theoretical weight: 25.64 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q13485 (Residues: 319-552; Coverage: 42%)
Gene names: DPC4, MADH4, SMAD4
Sequence domains: MH2 domain
Structure domains: Tumour Suppressor Smad4
Ski oncogene Chains: C, D
Molecule details ›
Chains: C, D
Length: 99 amino acids
Theoretical weight: 11.52 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P12755 (Residues: 219-313; Coverage: 13%)
Gene name: SKI
Structure domains: SAND domain-like

Ligands and Environments

1 bound ligand:
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X25
Spacegroup: P3221
Unit cell:
a: 109.8Å b: 109.8Å c: 141.1Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.235 0.231 0.28
Expression system: Escherichia coli