7N5O: Tyrosine-protein kinase BTK

Fragment-Based Discovery of a Novel Bruton's Tyrosine Kinase Inhibitor. Determined by X-ray diffraction at 1.25 Å resolution. Released 8 Sept 2021.

Method: X-ray diffraction
Resolution: 1.25 Å
Organism: Homo sapiens
Chains: 1
Atoms: 2,607
Mol. weight: 33.1 kDa
Ligands: 0BQ, PGO
Released: 8 Sept 2021

Explore 7N5O in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7N5O contains 18 α-helices and 12 β-strands across 1 chain. 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: 18 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	396	1	1
α-helix	399-401	3
β-strand	402-411	10	1
β-strand	414-421	8	1
β-strand	425-431	7	1
β-strand	437	1	2
α-helix	439-449	11
β-strand	457	1	3
α-helix	458-459	2
β-strand	460-464	5	1
β-strand	471-474	4	1
β-strand	481	1	3
α-helix	482-487	6
α-helix	489-491	3
α-helix	495-514	20
α-helix	524-526	3
β-strand	527-529	3	3
β-strand	535-537	3	3
α-helix	542-545	4
β-strand	546	1	2
α-helix	549-552	4
α-helix	561-563	3
α-helix	566-571	6
α-helix	576-591	16
α-helix	595-596	2
α-helix	603-611	9
α-helix	624-632	9
α-helix	638-640	3
α-helix	642-643	2
α-helix	644-657	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Tyrosine-protein kinase BTK	A	protein	283	Homo sapiens	Q06187 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>7N5O_1 Tyrosine-protein kinase BTK (chains A)
GPLPGKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGS
MSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQ
QLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG
SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRL
YRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES

Ligands and cofactors

ID	Name	Formula	Copies
0BQ	5-(1H-benzimidazol-2-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one	C9 H7 N5 O	1
PGO	S-1,2-propanediol	C3 H8 O2	1

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

Primary citation

Discovery of the Bruton's Tyrosine Kinase Inhibitor Clinical Candidate TAK-020 ( S )-5-(1-((1-Acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-2,4-dihydro-3 H -1,2,4-triazol-3-one, by Fragment-Based Drug Design. Sabat, M., Dougan, D.R., Knight, B. et al. J Med Chem (2021) 64:12893-12902. DOI 10.1021/acs.jmedchem.1c01026 · PubMed

Other PDB entries of the same protein (UniProt Q06187 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5P9J 1.08 Å, BTK1 cocrystallized with ibrutinib
6DI1 1.1 Å, Crystal structure of btk in complex with covalent fragment ligand
5P9I 1.11 Å, BTK1 soaked with ibrutinib-rev
6HRP 1.12 Å, CRYSTAL STRUCTURE OF BTK KINASE DOMAIN COMPLEXED WITH 6-(dimethylamino)-2-[2-(hydroxymeth…
6E4F 1.15 Å, Crystal structure of ARQ 531 in complex with the kinase domain of BTK
4RFZ 1.17 Å, Crystal structure of BTK kinase domain complexed with 6-(dimethylamino)-8-fluoro-2-[2-(hy…
7L5O 1.21 Å, Crystal structure of the noncovalently bonded complex of rilzabrutinib with BTK
5P9L 1.25 Å, BTK1 in complex with cc 292
6DI9 1.25 Å, Crystal structure of btk in complex with covalent inhibitor
6J6M 1.25 Å, Co-crystal structure of BTK kinase domain with Zanubrutinib
5P9K 1.28 Å, Crystal structure of btk with cnx 774
6BLN 1.3 Å, BTK complex with compound 13

Browse structure collections

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