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- PDB-10pi: JAK1 kinase (JH1 domain) in complex with povorcitinib -

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Basic information

Entry
Database: PDB / ID: 10pi
TitleJAK1 kinase (JH1 domain) in complex with povorcitinib
ComponentsTyrosine-protein kinase JAK1
KeywordsTRANSFERASE / Inhibitor / Kinase / Complex
Function / homology
Function and homology information


protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / type III interferon-mediated signaling pathway / T-helper 17 cell lineage commitment / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-7-mediated signaling pathway / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway ...protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / type III interferon-mediated signaling pathway / T-helper 17 cell lineage commitment / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-7-mediated signaling pathway / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway / interleukin-10-mediated signaling pathway / positive regulation of homotypic cell-cell adhesion / interleukin-15-mediated signaling pathway / Interleukin-15 signaling / Interleukin-12 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-27 signaling / Interleukin-35 Signalling / growth hormone receptor binding / Interleukin-2 signaling / Other interleukin signaling / Interleukin-20 family signaling / extrinsic component of cytoplasmic side of plasma membrane / Interleukin-6 signaling / IFNG signaling activates MAPKs / interleukin-6-mediated signaling pathway / interleukin-2-mediated signaling pathway / type I interferon-mediated signaling pathway / MAPK3 (ERK1) activation / positive regulation of sprouting angiogenesis / MAPK1 (ERK2) activation / Interleukin-10 signaling / Regulation of IFNA/IFNB signaling / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / cell surface receptor signaling pathway via JAK-STAT / Signaling by CSF3 (G-CSF) / Interleukin-7 signaling / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / cellular response to virus / Inactivation of CSF3 (G-CSF) signaling / positive regulation of protein localization to nucleus / Evasion by RSV of host interferon responses / ISG15 antiviral mechanism / Interferon gamma signaling / cytoplasmic side of plasma membrane / cytokine-mediated signaling pathway / Interferon alpha/beta signaling / RAF/MAP kinase cascade / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / protein phosphatase binding / Potential therapeutics for SARS / protein phosphorylation / cell differentiation / signaling receptor complex / endosome / intracellular signal transduction / response to antibiotic / focal adhesion / ubiquitin protein ligase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP binding / metal ion binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Tyrosine-protein kinase, non-receptor Jak1 / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : / Jak1 pleckstrin homology-like domain / FERM F2 acyl-CoA binding protein-like domain / FERM F1 ubiquitin-like domain / SH2 domain ...Tyrosine-protein kinase, non-receptor Jak1 / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : / Jak1 pleckstrin homology-like domain / FERM F2 acyl-CoA binding protein-like domain / FERM F1 ubiquitin-like domain / SH2 domain / FERM central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Tyrosine-protein kinase JAK1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.54 Å
AuthorsEpling, L.B. / Fenalti, G.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: J.Med.Chem. / Year: 2026
Title: Discovery of the Orally Bioavailable Isoform Selective Janus Kinase 1 (JAK1) Compound Povorcitinib (INCB054707) for the Treatment of Inflammatory and Autoimmune Diseases.
Authors: Zhuo, J. / Li, Y.L. / Qian, D.Q. / Burns, D.M. / Mei, S. / Rafalski, M. / Xu, M. / Cao, G. / Pan, Y. / Jia, Z. / Jalluri, R. / Epling, L.B. / Fenalti, G. / Deller, M.C. / Procak, J. / ...Authors: Zhuo, J. / Li, Y.L. / Qian, D.Q. / Burns, D.M. / Mei, S. / Rafalski, M. / Xu, M. / Cao, G. / Pan, Y. / Jia, Z. / Jalluri, R. / Epling, L.B. / Fenalti, G. / Deller, M.C. / Procak, J. / Covington, M. / He, X. / Collins, R. / Stubbs, M. / Burke, K. / Oliver, J. / Margulis, A. / Boer, J. / Wynn, R. / Scherle, P. / Diamond, S. / Newton, R. / Zhang, Y. / Metcalf, B. / Yao, W.
History
DepositionJan 30, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 10, 2026Provider: repository / Type: Initial release
Revision 1.1Jun 17, 2026Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Tyrosine-protein kinase JAK1
B: Tyrosine-protein kinase JAK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,70524
Polymers68,4322
Non-polymers2,27222
Water14,376798
1
A: Tyrosine-protein kinase JAK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,22010
Polymers34,2161
Non-polymers1,0049
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein kinase JAK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,48514
Polymers34,2161
Non-polymers1,26813
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)176.897, 49.489, 85.807
Angle α, β, γ (deg.)90.000, 118.431, 90.000
Int Tables number5
Space group name H-MC121
Space group name HallC2y
Components on special symmetry positions
IDModelComponents
11A-1973-

HOH

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Components

#1: Protein Tyrosine-protein kinase JAK1 / Janus kinase 1 / JAK-1


Mass: 34216.223 Da / Num. of mol.: 2 / Fragment: JH1 domain
Source method: isolated from a genetically manipulated source
Details: C terminal non / Source: (gene. exp.) Homo sapiens (human) / Gene: JAK1, JAK1A, JAK1B / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P23458, non-specific protein-tyrosine kinase
#2: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 19 / Source method: obtained synthetically / Formula: C2H6O2
#3: Chemical ChemComp-A1C68 / 4-{3-(cyanomethyl)-3-[(4M)-3',5'-dimethyl-1H,1'H-[4,4'-bipyrazol]-1-yl]azetidin-1-yl}-2,5-difluoro-N-[(2S)-1,1,1-trifluoropropan-2-yl]benzamide


Mass: 507.459 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H22F5N7O / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 798 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

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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: 2.42 Å3/Da / Density % sol: 49.07 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.1 M BIS-TRIS-Propane, pH 8.50, 20 % (w/v) PEG 3350, 5 mM K2-H-Phosphate, 5 mM K-H2-Phosphate, 5 mM Na2-H-Phosphate, 5 mM Na-H2-Phosphate

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 0.8856 Å
DetectorType: DECTRIS EIGER2 X CdTe 16M / Detector: PIXEL / Date: May 28, 2024
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.8856 Å / Relative weight: 1
ReflectionResolution: 1.54→29.34 Å / Num. obs: 94440 / % possible obs: 97.7 % / Redundancy: 2.9 % / Biso Wilson estimate: 18.31 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.07 / Rpim(I) all: 0.05 / Rrim(I) all: 0.08 / Net I/σ(I): 7.3
Reflection shellResolution: 1.54→1.58 Å / Redundancy: 3 % / Rmerge(I) obs: 0.6 / Num. unique obs: 13625 / CC1/2: 0.81 / Rpim(I) all: 0.4 / Rrim(I) all: 0.72 / % possible all: 97.1

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Processing

Software
NameVersionClassification
PHENIX1.21.2_5419refinement
autoPROCdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.54→29.34 Å / SU ML: 0.2 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 25.2452
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2119 4672 4.95 %
Rwork0.178 89720 -
obs0.1798 94392 97.4 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 32.14 Å2
Refinement stepCycle: LAST / Resolution: 1.54→29.34 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4630 0 155 798 5583
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0155066
X-RAY DIFFRACTIONf_angle_d1.49056843
X-RAY DIFFRACTIONf_chiral_restr0.0903727
X-RAY DIFFRACTIONf_plane_restr0.0198915
X-RAY DIFFRACTIONf_dihedral_angle_d8.0515760
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.54-1.560.4251360.35142993X-RAY DIFFRACTION96.78
1.56-1.580.35451450.32562921X-RAY DIFFRACTION96.78
1.58-1.60.32571540.30382989X-RAY DIFFRACTION96.68
1.6-1.620.2861230.27192948X-RAY DIFFRACTION96.82
1.62-1.640.28231520.26512966X-RAY DIFFRACTION96.98
1.64-1.660.2951630.25912942X-RAY DIFFRACTION96.88
1.66-1.680.29351490.24422989X-RAY DIFFRACTION97.09
1.68-1.710.29441620.23622955X-RAY DIFFRACTION97.32
1.71-1.730.27611760.23092949X-RAY DIFFRACTION97.08
1.73-1.760.22671250.21732975X-RAY DIFFRACTION97.3
1.76-1.790.2751400.22772985X-RAY DIFFRACTION97.38
1.79-1.830.25481680.22482983X-RAY DIFFRACTION97.22
1.83-1.860.26031700.20832942X-RAY DIFFRACTION97.01
1.86-1.90.23351560.19592983X-RAY DIFFRACTION97.24
1.9-1.940.20941300.18822950X-RAY DIFFRACTION96.43
1.94-1.990.22821360.18652902X-RAY DIFFRACTION94
1.99-2.030.23831350.17782979X-RAY DIFFRACTION97.16
2.03-2.090.22081550.18232986X-RAY DIFFRACTION97.43
2.09-2.150.22171570.18043033X-RAY DIFFRACTION98.03
2.15-2.220.21751750.18622968X-RAY DIFFRACTION98.4
2.22-2.30.23841950.17483003X-RAY DIFFRACTION98.55
2.3-2.390.22671930.17752960X-RAY DIFFRACTION98.47
2.39-2.50.22392100.16992982X-RAY DIFFRACTION98.37
2.5-2.630.21191400.17053073X-RAY DIFFRACTION98.56
2.63-2.80.25471450.16963023X-RAY DIFFRACTION98.32
2.8-3.010.20151200.17573058X-RAY DIFFRACTION98.18
3.01-3.320.1871680.16553054X-RAY DIFFRACTION97.73
3.32-3.80.17161710.14462971X-RAY DIFFRACTION96.62
3.8-4.780.16171760.13343084X-RAY DIFFRACTION99.15
4.78-29.340.18011470.17173174X-RAY DIFFRACTION98.08

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