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- PDB-28zs: Crystal structure of human DHX8 in complex with compound 53 and ADP -

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Basic information

Entry
Database: PDB / ID: 28zs
TitleCrystal structure of human DHX8 in complex with compound 53 and ADP
ComponentsGlutathione S-transferase class-mu 26 kDa isozyme,ATP-dependent RNA helicase DHX8
KeywordsRNA BINDING PROTEIN / Helicase / RNA / Splicing / Inhibitor / Cancer
Function / homology
Function and homology information


ATP-dependent activity, acting on RNA / U2-type catalytic step 2 spliceosome / glutathione transferase / glutathione transferase activity / RNA processing / catalytic step 2 spliceosome / spliceosomal complex / mRNA Splicing - Major Pathway / RNA splicing / glutathione metabolic process ...ATP-dependent activity, acting on RNA / U2-type catalytic step 2 spliceosome / glutathione transferase / glutathione transferase activity / RNA processing / catalytic step 2 spliceosome / spliceosomal complex / mRNA Splicing - Major Pathway / RNA splicing / glutathione metabolic process / mRNA splicing, via spliceosome / RNA helicase activity / RNA helicase / ATP hydrolysis activity / RNA binding / nucleoplasm / ATP binding / identical protein binding / nucleus
Similarity search - Function
DHX8/ Prp22, DEXH-box helicase domain / : / : / : / Helicase associated domain (HA2), ratchet-like / DEAD-box helicase, OB fold / Oligonucleotide/oligosaccharide-binding (OB)-fold / Helicase associated domain (HA2), winged-helix / Helicase-associated domain / Helicase associated domain (HA2) Add an annotation ...DHX8/ Prp22, DEXH-box helicase domain / : / : / : / Helicase associated domain (HA2), ratchet-like / DEAD-box helicase, OB fold / Oligonucleotide/oligosaccharide-binding (OB)-fold / Helicase associated domain (HA2), winged-helix / Helicase-associated domain / Helicase associated domain (HA2) Add an annotation / Glutathione S-transferase, C-terminal domain / : / DNA/RNA helicase, ATP-dependent, DEAH-box type, conserved site / DEAH-box subfamily ATP-dependent helicases signature. / Glutathione S-transferase, N-terminal domain / Glutathione S-transferase, C-terminal / Glutathione transferase family / Glutathione S-transferase, C-terminal-like / Soluble glutathione S-transferase C-terminal domain profile. / Soluble glutathione S-transferase N-terminal domain profile. / Glutathione S-transferase, N-terminal / S1 domain profile. / Glutathione S-transferase, C-terminal domain superfamily / Ribosomal protein S1-like RNA-binding domain / S1 RNA binding domain / DEAD/DEAH box helicase domain / DEAD/DEAH box helicase / S1 domain / Helicase conserved C-terminal domain / helicase superfamily c-terminal domain / Thioredoxin-like superfamily / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Nucleic acid-binding, OB-fold / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
: / ADENOSINE-5'-DIPHOSPHATE / Glutathione S-transferase class-mu 26 kDa isozyme / ATP-dependent RNA helicase DHX8
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.5 Å
AuthorsGraedler, U. / Augustin, M. / Lammens, A. / van Montfort, R.L.M.
Funding support United Kingdom, Germany, 3items
OrganizationGrant numberCountry
Cancer Research UKC309/A8274 United Kingdom
Cancer Research UKC309/A11566 United Kingdom
Other private Germany
CitationJournal: J.Med.Chem. / Year: 2026
Title: Fragment-Based Discovery of Potent RNA-Competitive Inhibitors of the DEAH-Box RNA Helicase DHX8.
Authors: Read, B.J. / Ewens, C. / Gigante, F. / Thomas, J. / Felisberto-Rodrigues, C. / Alvarez Peres, S. / Tighe, C. / de Las Heras Ruiz, E. / Schiemann, K. / Malcolm, A.G. / McAndrew, P.C. / ...Authors: Read, B.J. / Ewens, C. / Gigante, F. / Thomas, J. / Felisberto-Rodrigues, C. / Alvarez Peres, S. / Tighe, C. / de Las Heras Ruiz, E. / Schiemann, K. / Malcolm, A.G. / McAndrew, P.C. / Stubbs, M. / Patani, H. / Costa, H.D.S. / Stoodley, K. / Pickard, L. / Busch, M. / Gunnell, E. / Silva, S. / Knopp, A. / Hallett, S.T. / Augustin, M. / Lammens, A. / Carter, M. / Meniconi, M. / Ballarotto, M. / Ainsley, J. / Meister, P. / Sethi, D. / Burke, R. / Scarpino, A. / Le Bihan, Y.V. / Gradler, U. / Blagg, J. / Workman, P. / Clarke, P.A. / Blum, A. / Esdar, C. / Bhalay, G. / van Montfort, R.L.M.
History
DepositionMar 3, 2026Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 2, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Glutathione S-transferase class-mu 26 kDa isozyme,ATP-dependent RNA helicase DHX8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)102,0127
Polymers100,9331
Non-polymers1,0786
Water3,603200
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1580 Å2
ΔGint-14 kcal/mol
Surface area26600 Å2
MethodPISA
Unit cell
Length a, b, c (Å)145.681, 71.013, 90.344
Angle α, β, γ (deg.)90.000, 121.830, 90.000
Int Tables number5
Space group name H-MC121

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Components

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Protein , 1 types, 1 molecules A

#1: Protein Glutathione S-transferase class-mu 26 kDa isozyme,ATP-dependent RNA helicase DHX8 / GST 26 / Sj26 antigen / SjGST / DEAH box protein 8 / RNA helicase HRH1


Mass: 100933.281 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pFastBac / Gene: DHX8, DDX8 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P08515, UniProt: Q14562, glutathione transferase, RNA helicase

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Non-polymers , 5 types, 206 molecules

#2: Chemical ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Comment: ADP, energy-carrying molecule*YM
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-A1J1K / 2-[(1R)-1-phenyl-2-[4-(propan-2-ylamino)phenyl]ethyl]sulfanylpyridine-3-carboxylic acid


Mass: 392.514 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H24N2O2S / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 200 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity % sol: 37.46 %
Crystal growTemperature: 291 K / Method: vapor diffusion / pH: 8.5
Details: 1 microliter of DHX8del550 at 3 mg/mL with 1 mM ADP and 1 mM MgCl2, plus 0.5 microliter of a crystallisation solution consisting of 18% (w/v) PEG 6000, 0.1 M CaCl2, 0.1 M Tris/HCl pH 8.5.
Temp details: Oscillation between 288-298K

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Dec 6, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→44.91 Å / Num. obs: 27019 / % possible obs: 99 % / Redundancy: 4.2 % / Biso Wilson estimate: 60.6 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.18 / Rpim(I) all: 0.099 / Rrim(I) all: 0.207 / Net I/σ(I): 6.1 / Num. measured all: 112758 / Scaling rejects: 106
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.5-2.64.31.5191303030530.3480.831.7391.299.1
9.01-44.914.10.05524906100.9970.0290.06218.199

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Phasing

PhasingMethod: molecular replacement

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Processing

Software
NameVersionClassificationNB
XDSdata reduction
Aimless0.8.2data scaling
PHASERphasing
BUSTER2.10.4 (26-JUL-2023)refinement
PDB_EXTRACT3.28data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→44.91 Å / Cor.coef. Fo:Fc: 0.916 / Cor.coef. Fo:Fc free: 0.911 / SU R Cruickshank DPI: 0.477 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.479 / SU Rfree Blow DPI: 0.273 / SU Rfree Cruickshank DPI: 0.276
RfactorNum. reflection% reflectionSelection details
Rfree0.2524 1336 4.95 %RANDOM
Rwork0.2122 ---
obs0.2142 27012 98.8 %-
Displacement parametersBiso max: 98.3 Å2 / Biso mean: 55.55 Å2 / Biso min: 18.4 Å2
Baniso -1Baniso -2Baniso -3
1-11.0519 Å20 Å20.6862 Å2
2--11.6024 Å20 Å2
3----22.6544 Å2
Refine analyzeLuzzati coordinate error obs: 0.35 Å
Refinement stepCycle: final / Resolution: 2.5→44.91 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4873 0 68 202 5143
Biso mean--59.62 52.57 -
Num. residues----626
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1755SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes861HARMONIC5
X-RAY DIFFRACTIONt_it5054HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion689SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies4HARMONIC1
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact4183SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d5054HARMONIC20.007
X-RAY DIFFRACTIONt_angle_deg6863HARMONIC20.9
X-RAY DIFFRACTIONt_omega_torsion2.74
X-RAY DIFFRACTIONt_other_torsion17.53
LS refinement shellResolution: 2.5→2.52 Å / Rfactor Rfree error: 0 / Total num. of bins used: 51
RfactorNum. reflection% reflection
Rfree0.3585 25 4.62 %
Rwork0.3335 516 -
all0.3347 541 -
obs--98.88 %
Refinement TLS params.Method: refined / Origin x: 31.5815 Å / Origin y: 0.5292 Å / Origin z: 27.6621 Å
111213212223313233
T-0.0018 Å2-0.0253 Å20.0412 Å2--0.1059 Å2-0.004 Å2---0.0737 Å2
L0.5216 °2-0.1064 °20.1141 °2-0.881 °20.244 °2--0.5863 °2
S-0.0586 Å °0.0001 Å °0.0196 Å °-0.0822 Å °0.0686 Å °-0.0158 Å °-0.0337 Å °-0.0616 Å °-0.01 Å °
Refinement TLS groupSelection details: { A|* }

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