8S9A: TYK2 pseudokinase domain

Crystal structure of the TYK2 pseudokinase domain in complex with TAK-279. Determined by X-ray diffraction at 1.83 Å resolution. Released 26 Jul 2023.

Method: X-ray diffraction
Resolution: 1.83 Å
Organism: Homo sapiens
Chains: 3
Atoms: 7,174
Mol. weight: 101.5 kDa
Ligands: ZSB
Released: 26 Jul 2023

Explore 8S9A in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8S9A contains 54 α-helices and 30 β-strands across 3 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 20 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	582	1
β-strand	583	1	1
α-helix	584-585	2
α-helix	586-588	3
β-strand	589-598	10	1
β-strand	601-609	9	1
β-strand	636-644	9	1
α-helix	645	1
α-helix	649-664	16
β-strand	670	1	2
β-strand	673-679	7	1
β-strand	682-688	7	1
β-strand	694	1	2
α-helix	695-701	7
α-helix	708-728	21
α-helix	737-739	3
β-strand	740-744	5	2
β-strand	754-757	4	2
α-helix	758-759	2
α-helix	764-766	3
α-helix	769-774	6
α-helix	781-783	3
α-helix	794-808	15
α-helix	812-813	2
α-helix	820-828	9
α-helix	831-836	6
α-helix	839-848	10
α-helix	853-855	3
α-helix	857-858	2
α-helix	859-866	8

Chain B: 17 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	583-584	2	3
α-helix	586-588	3
β-strand	589-598	10	3
β-strand	601-609	9	3
β-strand	636-644	9	3
α-helix	645	1
α-helix	649-663	15
β-strand	670	1	4
β-strand	673-679	7	3
β-strand	682-688	7	3
β-strand	694	1	4
α-helix	695-701	7
α-helix	708-727	20
α-helix	737-739	3
β-strand	740-744	5	4
β-strand	754-757	4	4
α-helix	758-759	2
α-helix	764-766	3
α-helix	769-774	6
α-helix	781-783	3
α-helix	794-808	15
α-helix	820-828	9
α-helix	831-836	6
α-helix	839-848	10
α-helix	853-855	3
α-helix	857-858	2
α-helix	859-866	8

Chain C: 17 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	583-584	2	5
α-helix	586-588	3
β-strand	589-598	10	5
β-strand	601-608	8	5
β-strand	637-644	8	5
α-helix	645	1
α-helix	649-664	16
β-strand	670	1	6
β-strand	673-679	7	5
β-strand	682-688	7	5
β-strand	694	1	6
α-helix	695-701	7
α-helix	708-728	21
α-helix	737-739	3
β-strand	740-744	5	6
β-strand	754-757	4	6
α-helix	758-759	2
α-helix	764-766	3
α-helix	769-774	6
α-helix	781-783	3
α-helix	794-808	15
α-helix	820-828	9
α-helix	831-835	5
α-helix	839-848	10
α-helix	853-855	3
α-helix	857-858	2
α-helix	859-866	8

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Non-receptor tyrosine-protein kinase TYK2	A, B, C	protein	295	Homo sapiens	P29597 (AlphaFold model)

Sequence of entity 1 (A, B, C), FASTA

>8S9A_1 Non-receptor tyrosine-protein kinase TYK2 (chains A, B, C)
NLSQLSFHRVDQKEITQLSHLGQGTRTNVYEGRLRVEGSGDPEEGKMDDEDPLVPGRDRG
QELRVVLKVLDPSHHDIALAFYETASLMSQVSHTHLAFVHGVCVRGPENIMVTEYVEHGP
LDVWLRRERGHVPMAWKMVVAQQLASALSYLENKNLVHGNVCGRNILLARLGLAEGTSPF
IKLSDPGVGLGALSREERVERIPWLAPECLPGGANSLSTAMDKWGFGATLLEICFDGEAP
LQSRSPSEKEHFYQRQHRLPEPSCPQLATLTSQCLTYEPTQRPSFRTILRDLTRL

Ligands and cofactors

ID	Name	Formula	Copies
ZSB	(8S)-N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-{[(1P,2'P)-2-oxo-2H-[1,2…	C23 H24 N8 O3	3

Water and common crystallization additives (EDO, ACT) are not listed.

Primary citation

Discovery of a Potent and Selective Tyrosine Kinase 2 Inhibitor: TAK-279. Leit, S., Greenwood, J., Carriero, S. et al. J Med Chem (2023) 66:10473-10496. DOI 10.1021/acs.jmedchem.3c00600 · PubMed

Other PDB entries of the same protein (UniProt P29597 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3LXP 1.65 Å, Structural and Thermodynamic Characterization of the TYK2 and JAK3 Kinase Domains in…
8S99 1.71 Å, Crystal structure of the TYK2 pseudokinase domain in complex with compound 11
4WOV 1.8 Å, Crystal structure of tyrosine kinase 2 JH2 (pseudo kinase domain) complexed with bms-066…
8S98 1.87 Å, Crystal structure of the TYK2 pseudokinase domain in complex with compound 8
5C03 1.9 Å, Crystal Structure of kinase
5TKD 1.92 Å, Crystal structure of tyrosine kinase 2 JH2 (pseudo kinase domain) complexed with…
6NZE 1.96 Å, Crystal structure of tyrosine kinase 2 JH2 (pseudo kinase domain) complexed with…
8TB6 1.96 Å, TYK2 JH2 bound to Compound14
6AAM 1.98 Å, Crystal structure of TYK2 in complex with peficitinib
4PO6 1.99 Å, Crystal structure of the human TYK2 FERM and SH2 domains with an IFNAR1 intracellular…
3NZ0 2.0 Å, Non-phosphorylated TYK2 kinase with CMP6
4GIH 2.0 Å, Tyk2 (JH1) in complex with 2,6-DICHLORO-N-{2-[(CYCLOPROPYLCARBONYL)AMINO]PYRIDIN-4-YL}BEN…

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