4RFZ: BTK kinase domain

Crystal structure of BTK kinase domain complexed with 6-(dimethylamino)-8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-(morpholine-4-carbonyl)-2-pyridyl]amino]-6-oxo-3-pyridyl]phenyl]isoquinolin-1-one. Determined by X-ray diffraction at 1.17 Å resolution. Released 24 Dec 2014.

Method: X-ray diffraction
Resolution: 1.17 Å
Organism: Homo sapiens
Chains: 1
Atoms: 2,487
Mol. weight: 33.3 kDa
Ligands: 3OV
Released: 24 Dec 2014

Explore 4RFZ in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

4RFZ contains 19 α-helices and 11 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: 19 helices, 11 β-strands

Element	Residues	Length	Sheet
α-helix	399-401	3
β-strand	402-411	10	1
β-strand	414-421	8	1
β-strand	425-431	7	1
α-helix	432-433	2
β-strand	437	1	2
α-helix	439-450	12
β-strand	457	1	3
β-strand	460-464	5	1
β-strand	471-475	5	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	616-619	4
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

>4RFZ_1 Tyrosine-protein kinase BTK (chains A)
GSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGS
MSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREARHAFQTQ
QLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVG
SKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRL
YRPHLASAAVYTIMYSCWHEKADERPTFKILLSNILDVMDEES

Ligands and cofactors

ID	Name	Formula	Copies
3OV	6-(dimethylamino)-8-fluoro-2-[2-(hydroxymethyl)-3-(1-methyl-5-{[5-(morpholin-4-…	C34 H33 F N6 O5	1

Water and common crystallization additives (DMS) are not listed.

Primary citation

Finding the perfect spot for fluorine: Improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold. Lou, Y., Sweeney, Z.K., Kuglstatter, A. et al. Bioorg Med Chem Lett (2015) 25:367-371. DOI 10.1016/j.bmcl.2014.11.030 · 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
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
7N5O 1.25 Å, Fragment-Based Discovery of a Novel Bruton's Tyrosine Kinase Inhibitor
5P9K 1.28 Å, Crystal structure of btk with cnx 774
6BLN 1.3 Å, BTK complex with compound 13

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