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- PDB-9du1: Co-crystal structure of the ternary complex of human FKBP12, BRD9... -

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Basic information

Entry
Database: PDB / ID: 9du1
TitleCo-crystal structure of the ternary complex of human FKBP12, BRD9 bromo domain and Compound 1
Components
  • Bromodomain-containing protein 9
  • Peptidyl-prolyl cis-trans isomerase FKBP1A
KeywordsLIGASE / FKBP12 / BRD9 / bromo domain / glue degrader
Function / homology
Function and homology information


macrolide binding / activin receptor binding / regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion / transforming growth factor beta receptor binding / cytoplasmic side of membrane / TGFBR1 LBD Mutants in Cancer / type I transforming growth factor beta receptor binding / GBAF complex / negative regulation of activin receptor signaling pathway / heart trabecula formation ...macrolide binding / activin receptor binding / regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion / transforming growth factor beta receptor binding / cytoplasmic side of membrane / TGFBR1 LBD Mutants in Cancer / type I transforming growth factor beta receptor binding / GBAF complex / negative regulation of activin receptor signaling pathway / heart trabecula formation / I-SMAD binding / regulation of amyloid precursor protein catabolic process / signaling receptor inhibitor activity / terminal cisterna / ryanodine receptor complex / SWI/SNF complex / 'de novo' protein folding / ventricular cardiac muscle tissue morphogenesis / FK506 binding / positive regulation of stem cell population maintenance / TGF-beta receptor signaling activates SMADs / mTORC1-mediated signalling / regulation of ryanodine-sensitive calcium-release channel activity / Calcineurin activates NFAT / negative regulation of cell differentiation / regulation of immune response / heart morphogenesis / supramolecular fiber organization / : / sarcoplasmic reticulum membrane / T cell activation / protein maturation / sarcoplasmic reticulum / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / calcium channel regulator activity / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / negative regulation of transforming growth factor beta receptor signaling pathway / Z disc / SARS-CoV-1 activates/modulates innate immune responses / protein folding / regulation of protein localization / protein refolding / amyloid fibril formation / Potential therapeutics for SARS / nucleic acid binding / transmembrane transporter binding / positive regulation of canonical NF-kappaB signal transduction / chromatin remodeling / positive regulation of cell population proliferation / regulation of transcription by RNA polymerase II / chromatin / nucleoplasm / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
Protein of unknown function DUF3512 / Domain of unknown function (DUF3512) / : / : / FKBP-type peptidyl-prolyl cis-trans isomerase / FKBP-type peptidyl-prolyl cis-trans isomerase domain / FKBP-type peptidyl-prolyl cis-trans isomerase domain profile. / Peptidyl-prolyl cis-trans isomerase domain superfamily / Bromodomain / bromo domain ...Protein of unknown function DUF3512 / Domain of unknown function (DUF3512) / : / : / FKBP-type peptidyl-prolyl cis-trans isomerase / FKBP-type peptidyl-prolyl cis-trans isomerase domain / FKBP-type peptidyl-prolyl cis-trans isomerase domain profile. / Peptidyl-prolyl cis-trans isomerase domain superfamily / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily
Similarity search - Domain/homology
: / Peptidyl-prolyl cis-trans isomerase FKBP1A / Bromodomain-containing protein 9
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.01 Å
AuthorsRomanowski, M.J. / Viscomi, J.S.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: To Be Published
Title: Ternary complex DNA-encoded library screening uncovers FKBP molecular glues
Authors: Zandi, T.A. / Tan, Z.R. / Romanowski, M.J. / Viscomi, J.S. / Tong, B.Q. / Bonazzi, S. / Zecri, F.J. / Schreiber, S.L. / Michaud, G.A.
History
DepositionOct 2, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 8, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Peptidyl-prolyl cis-trans isomerase FKBP1A
B: Peptidyl-prolyl cis-trans isomerase FKBP1A
C: Peptidyl-prolyl cis-trans isomerase FKBP1A
D: Peptidyl-prolyl cis-trans isomerase FKBP1A
E: Bromodomain-containing protein 9
F: Bromodomain-containing protein 9
G: Bromodomain-containing protein 9
H: Bromodomain-containing protein 9
hetero molecules


Theoretical massNumber of molelcules
Total (without water)105,25413
Polymers101,5138
Non-polymers3,7415
Water14,250791
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)59.163, 97.512, 100.002
Angle α, β, γ (deg.)90.00, 93.69, 90.00
Int Tables number4
Space group name H-MP1211

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Components

#1: Protein
Peptidyl-prolyl cis-trans isomerase FKBP1A / PPIase FKBP1A / 12 kDa FK506-binding protein / 12 kDa FKBP / FKBP-12 / Calstabin-1 / FK506-binding ...PPIase FKBP1A / 12 kDa FK506-binding protein / 12 kDa FKBP / FKBP-12 / Calstabin-1 / FK506-binding protein 1A / FKBP-1A / Immunophilin FKBP12 / Rotamase


Mass: 12054.782 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62942, peptidylprolyl isomerase
#2: Protein
Bromodomain-containing protein 9 / Rhabdomyosarcoma antigen MU-RMS-40.8


Mass: 13323.455 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9H8M2
#3: Chemical
ChemComp-A1BB8 / 4-[4-{cyclopropyl[(1-methyl-1H-pyrazol-4-yl)methyl]amino}-6-({1-[(2R)-2-{[(2S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carbonyl]amino}-4-(4-methoxyphenyl)butanoyl]piperidin-4-yl}amino)-1,3,5-triazin-2-yl]-N-ethylpiperazine-1-carboxamide


Mass: 912.134 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C47H69N13O6 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 791 / Source method: isolated from a natural source / Formula: H2O
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 Matthews: 2.84 Å3/Da / Density % sol: 56.62 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 0.1 M HEPES PH 7.5, 20% PEG 8000 (MCSG SCREEN 1, CONDITION A1); 1:1:1 FKBP12:BRD9:MOTHER LIQUOR PLUS EQUIMOLAR COMPOUND IN 200-NL DROP. COMPLEX CONCENTRATED TO 10 MG/ML

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P13 (MX1) / Wavelength: 0.97626 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 19, 2024
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97626 Å / Relative weight: 1
ReflectionResolution: 2.01→99.8 Å / Num. obs: 71892 / % possible obs: 99.8 % / Redundancy: 7.1 % / CC1/2: 0.991 / Net I/σ(I): 5.7
Reflection shellResolution: 2.01→2.014 Å / Num. unique obs: 755 / CC1/2: 0.324

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Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.01→59.04 Å / SU ML: 0.29 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 30.32 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2588 3621 5.11 %
Rwork0.2236 --
obs0.2254 70867 93.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.01→59.04 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6631 0 270 791 7692
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.007
X-RAY DIFFRACTIONf_angle_d1.397
X-RAY DIFFRACTIONf_dihedral_angle_d19.3021012
X-RAY DIFFRACTIONf_chiral_restr0.074995
X-RAY DIFFRACTIONf_plane_restr0.0111223
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.01-2.040.3551400.35072500X-RAY DIFFRACTION91
2.04-2.060.3846960.33611957X-RAY DIFFRACTION88
2.07-2.090.3078851730X-RAY DIFFRACTION92
2.09-2.130.33111630.31192758X-RAY DIFFRACTION99
2.13-2.160.36951520.3122707X-RAY DIFFRACTION99
2.16-2.190.35541620.29662722X-RAY DIFFRACTION99
2.19-2.230.32721400.29692675X-RAY DIFFRACTION99
2.23-2.270.33241350.29462271X-RAY DIFFRACTION82
2.27-2.320.35091290.27662698X-RAY DIFFRACTION99
2.32-2.360.30041250.26942760X-RAY DIFFRACTION99
2.36-2.410.32741480.27942659X-RAY DIFFRACTION98
2.41-2.470.34381480.26652745X-RAY DIFFRACTION99
2.47-2.530.28871740.25742723X-RAY DIFFRACTION100
2.53-2.60.28271760.24792686X-RAY DIFFRACTION100
2.6-2.680.2691080.24531941X-RAY DIFFRACTION71
2.68-2.760.24261230.23452723X-RAY DIFFRACTION99
2.76-2.860.2731490.23482768X-RAY DIFFRACTION100
2.86-2.980.27921690.24272725X-RAY DIFFRACTION100
2.98-3.110.34311500.23852750X-RAY DIFFRACTION100
3.11-3.280.25311510.22212733X-RAY DIFFRACTION100
3.28-3.480.23021320.20422449X-RAY DIFFRACTION88
3.48-3.750.24911400.19892516X-RAY DIFFRACTION92
3.75-4.130.1991590.18422632X-RAY DIFFRACTION96
4.13-4.730.18971240.16482784X-RAY DIFFRACTION100
4.73-5.950.21621110.18032823X-RAY DIFFRACTION99
5.95-100.17741322811X-RAY DIFFRACTION99

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