4jtc

X-ray diffraction
2.56Å resolution

Crystal structure of Kv1.2-2.1 paddle chimera channel in complex with Charybdotoxin in Cs+

Released:

Function and Biology Details

Reactions catalysed:
Succinyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-succinyldihydrolipoyl)lysine
Phosphoenolpyruvate + D-erythrose 4-phosphate + H(2)O = 3-deoxy-D-arabino-hept-2-ulosonate 7-phosphate + phosphate
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
1-(5-phospho-beta-D-ribosyl)-5-((5-phospho-beta-D-ribosylamino)methylideneamino)imidazole-4-carboxamide = 5-((5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino)-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide
1-(5-phospho-beta-D-ribosyl)-ATP + diphosphate = ATP + 5-phospho-alpha-D-ribose 1-diphosphate
3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholanate + NAD(+) = 3-alpha,12-alpha-dihydroxy-7-oxo-5-beta-cholanate + NADH
S-adenosyl-L-methionine + adenine in DNA = S-adenosyl-L-homocysteine + N-6-methyladenine in DNA 
(S)-2-hydroxy acid + O(2) = 2-oxo acid + H(2)O(2)
ATP = 3',5'-cyclic AMP + diphosphate
Acyl-CoA + H(2)O = CoA + a carboxylate
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.
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.
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
S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid
4 benzenediol + O(2) = 4 benzosemiquinone + 2 H(2)O
Triacylglycerol + H(2)O = diacylglycerol + a carboxylate
Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO(2) + [acyl-carrier-protein]
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.
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
2 glutathione + ROOH = glutathione 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(+)
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
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'.
(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.
4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate
NTP + H(2)O = NDP + phosphate
ATP + H(2)O + 4 H(+)(Side 1) = ADP + phosphate + 4 H(+)(Side 2)
N-(5-phospho-beta-D-ribosyl)anthranilate = 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine
A beta-lactam + H(2)O = a substituted beta-amino acid
2 3-phospho-D-glycerate + 2 H(+) = D-ribulose 1,5-bisphosphate + CO(2) + H(2)O
RX + glutathione = HX + R-S-glutathione
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
D-glucarate = 5-dehydro-4-deoxy-D-glucarate + H(2)O
D-glyceraldehyde 3-phosphate = glycerone phosphate
S-adenosyl 3-(methylthio)propylamine + putrescine = 5'-S-methyl-5'-thioadenosine + spermidine
D-xylopyranose = D-xylulose
2-dehydro-3-deoxy-6-phosphate-D-gluconate = pyruvate + D-glyceraldehyde 3-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)
A (Z)-hexadec-9-enoyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein] = a (Z)-3-oxooctadec-11-enoyl-[acyl-carrier protein] + CO(2) + an [acyl-carrier protein]
NAD(+) + glycine + sulfide = nicotinamide + ADP-5-ethyl-4-methylthiazole-2-carboxylate + 3 H(2)O
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.
Cutin + H(2)O = cutin monomers
5-methyltetrahydrofolate + NAD(P)(+) = 5,10-methylenetetrahydrofolate + NAD(P)H
2 bilirubin + O(2) = 2 biliverdin + 2 H(2)O
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]
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
(S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA + NADH
L-aspartate 4-semialdehyde + phosphate + NADP(+) = L-4-aspartyl phosphate + NADPH
N-carbamoylputrescine + H(2)O = putrescine + CO(2) + NH(3)
(S)-malate = fumarate + H(2)O
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).
ATP + H(2)O = ADP + phosphate
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.
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Hydrolyzes single-stranded DNA or mismatched double-stranded DNA and polynucleotides, releasing free uracil
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
ATP + nucleoside diphosphate = ADP + nucleoside triphosphate
(S)-lactate + NAD(+) = pyruvate + NADH
ATP + AMP = 2 ADP
L-glutamate + H(2)O + NADP(+) = 2-oxoglutarate + NH(3) + NADPH
ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
Beta-D-ribopyranose = beta-D-ribofuranose
GDP-beta-L-fucose + NADP(+) = GDP-4-dehydro-alpha-D-rhamnose + NADPH
Naphthalene + NADH + O(2) = (1R,2S)-1,2-dihydronaphthalene-1,2-diol + NAD(+)
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.
Acetyl-CoA + L-serine = CoA + O-acetyl-L-serine
(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H(2)O
AMP + H(2)O = D-ribose 5-phosphate + adenine
ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide
Hydrolysis of terminal, non-reducing (1->4)-linked alpha-D-glucose residues with release of alpha-D-glucose
ATP + L-histidine + tRNA(His) = AMP + diphosphate + L-histidyl-tRNA(His)
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
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
Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
(2S)-2-amino-4-deoxychorismate + H(2)O = (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate + pyruvate
ATP + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly = diphosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP
Hydrolysis of terminal, non-reducing branched (1->3)-alpha-D-galactosidic residues, producing free D-galactose
L-threonine + ATP + HCO(3)(-) = L-threonylcarbamoyladenylate + diphosphate + H(2)O
2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate + CMP
ATP + a protein = ADP + a phosphoprotein
S-adenosyl-L-methionine + pseudouridine(1915) in 23S rRNA = S-adenosyl-L-homocysteine + N(3)-methylpseudouridine(1915) in 23S rRNA
Uridine + phosphate = uracil + alpha-D-ribose 1-phosphate 
UDP-N-acetyl-alpha-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-hex-4-ulose + H(2)O
H(2) + A = AH(2)
RH + [reduced NADPH--hemoprotein reductase] + O(2) = ROH + [oxidized NADPH--hemoprotein reductase] + 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
1-haloalkane + H(2)O = a primary alcohol + halide
A 4-O-methyl-D-glucopyranuronate ester + H(2)O = 4-O-methyl-D-glucuronic acid + an alcohol
N(2)-acetyl-L-ornithine + L-glutamate = L-ornithine + N-acetyl-L-glutamate
L-aspartate = D-aspartate
(R)-mandelonitrile = cyanide + benzaldehyde
A long-chain aldehyde + O(2) + 2 NADPH = an alkane + formate + H(2)O + 2 NADP(+)
L-asparagine + H(2)O = L-aspartate + NH(3)
L-cystathionine + H(2)O = L-homocysteine + NH(3) + pyruvate
ATP + UMP = ADP + UDP
(1a) S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-N(omega)-methyl-L-arginine
(1a) L-cystathionine = L-cysteine + 2-aminobut-2-enoate
(1a) NADP(+) = 2'-phospho-cyclic ADP-ribose + nicotinamide
(1a) S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [HECT-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine
N-acetyl-O-acetylneuraminate + H(2)O = N-acetylneuraminate + acetate
ATP + H(2)O + cellular protein(Side 1) = ADP + phosphate + cellular protein(Side 2)
(R)-10-hydroxystearate = oleate + H(2)O
Cellobiose = 4-O-beta-D-glucopyranosyl-D-mannose
An aldehyde + NAD(P)(+) + H(2)O = a carboxylate + NAD(P)H
ATP + succinate + CoA = ADP + phosphate + succinyl-CoA
Preferential cleavage at the carboxyl of hydrophobic amino acids, but fails to cleave 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 of insulin B chain. Activates trypsinogen, and degrades keratin.
Isocitrate = succinate + glyoxylate
A chalcone = a flavanone
L-arginine + H(2)O = L-ornithine + urea
Cleaves -Ala-|-Ser- and -Ala-|-Ala- bonds in the scaffold protein.
L-fuculose 1-phosphate = glycerone phosphate + (S)-lactaldehyde
ATP + pantetheine 4'-phosphate = diphosphate + 3'-dephospho-CoA
ATP + FMN = diphosphate + FAD
A carboxylic ester + H(2)O = an alcohol + a carboxylate
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.
Maleate = fumarate
2 phenolic donor + H(2)O(2) = 2 phenoxyl radical of the donor + 2 H(2)O
Peptidylproline (omega=180) = peptidylproline (omega=0)
Endohydrolysis of (1->4)-beta-D-xylosidic linkages in xylans
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = diphosphate + geranylgeranyl diphosphate
S-adenosyl-L-methionine + 5-carboxymethylaminomethyluridine(34) in tRNA(Leu) = S-adenosyl-L-homocysteine + 5-carboxymethylaminomethyl-2'-O-methyluridine(34) in tRNA(Leu)
ADP-alpha-D-glucose + D-glucose 6-phosphate = ADP + alpha,alpha-trehalose 6-phosphate
L-lysine = cadaverine + CO(2)
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
S-adenosyl-L-homocysteine + H(2)O = L-homocysteine + adenosine
Geranylgeranyl diphosphate = (+)-copalyl diphosphate
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.
ATP + riboflavin = ADP + FMN
Hydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose and similar substrates, releasing cellobiose from the reducing ends of the chains.
S-formylglutathione + H(2)O = glutathione + formate
An N-acyl-L-homoserine lactone + H(2)O = an N-acyl-L-homoserine
Acetyl-CoA + a 2-deoxystreptamine antibiotic = CoA + N(3)-acetyl-2-deoxystreptamine antibiotic
Exolytic cleavage of the (1->4)-beta-glycosidic linkage between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) residues in peptidoglycan, from either the reducing or the non-reducing ends of the peptidoglycan chains, with concomitant formation of a 1,6-anhydrobond in the MurNAc residue.
Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides
2'-deoxycytidine + H(2)O = 2'-deoxyuridine + NH(3)
L-glutamine + D-fructose 6-phosphate = L-glutamate + D-glucosamine 6-phosphate
ATP + pyridoxal = ADP + pyridoxal 5'-phosphate
ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol hexakisphosphate
(1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate = 2-succinylbenzoate + H(2)O
Pyridoxamine 5'-phosphate + H(2)O + O(2) = pyridoxal 5'-phosphate + NH(3) + H(2)O(2)
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
Pyruvate + L-aspartate-4-semialdehyde = (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate + H(2)O
(1a) NAD(+) = cyclic ADP-ribose + nicotinamide
5'-deoxyadenosine + H(2)O = 5-deoxy-D-ribose + adenine
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
Hydrolysis of terminal, non-reducing beta-D-mannose residues in beta-D-mannosides
N(6)-prenyladenine + acceptor + H(2)O = adenine + 3-methylbut-2-enal + reduced acceptor
2 superoxide + 2 H(+) = O(2) + H(2)O(2)
Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.
Blasticidin S + H(2)O = deaminohydroxyblasticidin S + NH(3)
2-lysophosphatidylcholine + H(2)O = glycerophosphocholine + a carboxylate
ATP + L-glutamate + NH(3) = ADP + phosphate + L-glutamine
Malonyl-CoA + an [acyl-carrier-protein] = CoA + a malonyl-[acyl-carrier-protein]
Oleoyl-[acyl-carrier-protein] + H(2)O = [acyl-carrier-protein] + oleate
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Palmitoyl-CoA + H(2)O = CoA + palmitate
A phenyl acetate + H(2)O = a phenol + acetate
ATP + acetyl-CoA + HCO(3)(-) = ADP + phosphate + malonyl-CoA
ATP + propanoyl-CoA + HCO(3)(-) = ADP + phosphate + (S)-methylmalonyl-CoA
NADPH + NAD(+) + H(+)(Side 1) = NADP(+) + H(+)(Side 2) + NADH

Structure analysis Details

Assemblies composition:
hetero octamer
hetero nonamer (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Voltage-gated potassium channel subunit beta-2 Chains: A, G
Molecule details ›
Chains: A, G
Length: 333 amino acids
Theoretical weight: 37.35 KDa
Source organism: Rattus norvegicus
Expression system: Komagataella pastoris
UniProt:
  • Canonical: P62483 (Residues: 36-367; Coverage: 91%)
Gene names: Ckbeta2, Kcnab2, Kcnb3
Sequence domains: Aldo/keto reductase family
Structure domains: NADP-dependent oxidoreductase domain
Potassium voltage-gated channel subfamily A member 2; Potassium voltage-gated channel subfamily B member 1 Chains: B, H
Molecule details ›
Chains: B, H
Length: 514 amino acids
Theoretical weight: 58.82 KDa
Source organism: Rattus norvegicus
Expression system: Komagataella pastoris
UniProt:
  • Canonical: P15387 (Residues: 30-30, 274-307; Coverage: 4%)
  • Canonical: P63142 (Residues: 1-31, 33-266, 305-499; Coverage: 92%)
Gene names: Kcna2, Kcnb1
Sequence domains:
Structure domains:
Potassium channel toxin alpha-KTx 1.1 Chain: Y
Molecule details ›
Chain: Y
Length: 37 amino acids
Theoretical weight: 4.31 KDa
Source organism: Leiurus quinquestriatus hebraeus
Expression system: Escherichia coli
UniProt:
  • Canonical: P13487 (Residues: 23-59; Coverage: 100%)
Sequence domains: Scorpion short toxin, BmKK2

Ligands and Environments


Cofactor: Ligand NAP 2 x NAP
2 bound ligands:
1 modified residue:

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X29A
Spacegroup: P4212
Unit cell:
a: 145.434Å b: 145.434Å c: 285.591Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.237 0.237 0.262
Expression systems:
  • Komagataella pastoris
  • Escherichia coli