8W3W: IRAK4

Crystal structure of IRAK4 in complex with compound 4. Determined by X-ray diffraction at 1.98 Å resolution. Released 1 May 2024.

Method: X-ray diffraction
Resolution: 1.98 Å
Organism: Homo sapiens
Chains: 4
Atoms: 9,879
Mol. weight: 147.6 kDa
Ligands: A1AFO
Released: 1 May 2024

Explore 8W3W in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8W3W contains 76 α-helices and 72 β-strands across 4 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.

Chains A and B: 19 helices, 18 β-strands

Element	Residues	Length	Sheet
β-strand	166-167	2	1
α-helix	170-176	7
β-strand	184	1	1
α-helix	185-187	3
β-strand	191-194	4	1
β-strand	198-205	8	1
β-strand	208-215	8	1
α-helix	223-239	17
β-strand	245	1	2
α-helix	246-247	2
β-strand	248-252	5	1
β-strand	259-263	5	1
β-strand	269	1	2
α-helix	270-274	5
α-helix	277-279	3
α-helix	280-284	5
α-helix	285-304	20
β-strand	307-308	2	3
α-helix	314-316	3
β-strand	317-319	3	2
β-strand	325-327	3	2
β-strand	334-335	2	3
β-strand	343-344	2	4
α-helix	352-354	3
α-helix	357-360	4
β-strand	363-364	2	4
α-helix	366-382	17
β-strand	387	1	5
β-strand	391	1	6
β-strand	395	1	5
α-helix	396-398	3
α-helix	399-404	6
α-helix	410-412	3
α-helix	423-436	14
α-helix	441-443	3
α-helix	445-446	2
α-helix	447-458	12

Chain C: 19 helices, 18 β-strands

Element	Residues	Length	Sheet
β-strand	166-167	2	13
α-helix	170-176	7
β-strand	184	1	13
α-helix	185-187	3
β-strand	191-194	4	13
β-strand	198-205	8	13
β-strand	208-215	8	13
α-helix	223-239	17
β-strand	245	1	14
α-helix	246-247	2
β-strand	248-252	5	13
β-strand	258-263	6	13
β-strand	269	1	14
α-helix	270-274	5
α-helix	277-279	3
α-helix	280-284	5
α-helix	285-304	20
β-strand	307-308	2	15
α-helix	314-316	3
β-strand	317-319	3	14
β-strand	325-327	3	14
β-strand	334-335	2	15
β-strand	343-344	2	16
α-helix	352-354	3
α-helix	357-360	4
β-strand	363-364	2	16
α-helix	366-382	17
β-strand	387	1	17
β-strand	391	1	12
β-strand	395	1	17
α-helix	396-398	3
α-helix	399-404	6
α-helix	410-412	3
α-helix	423-436	14
α-helix	441-443	3
α-helix	445-446	2
α-helix	447-458	12

Chain D: 19 helices, 18 β-strands

Element	Residues	Length	Sheet
β-strand	166-167	2	18
α-helix	170-176	7
β-strand	184	1	18
α-helix	185-187	3
β-strand	191-195	5	18
β-strand	198-205	8	18
β-strand	208-214	7	18
α-helix	223-239	17
β-strand	245	1	19
α-helix	246-247	2
β-strand	248-252	5	18
β-strand	259-263	5	18
β-strand	269	1	19
α-helix	270-274	5
α-helix	277-279	3
α-helix	280-284	5
α-helix	285-304	20
β-strand	307-308	2	20
α-helix	314-316	3
β-strand	317-319	3	19
β-strand	325-327	3	19
β-strand	334-335	2	20
β-strand	343-344	2	21
α-helix	352-354	3
α-helix	357-360	4
β-strand	363-364	2	21
α-helix	366-382	17
β-strand	387	1	22
β-strand	391	1	6
β-strand	395	1	22
α-helix	396-398	3
α-helix	399-404	6
α-helix	410-412	3
α-helix	423-436	14
α-helix	441-443	3
α-helix	445-446	2
α-helix	447-458	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Interleukin-1 receptor-associated kinase 4	A, B, C, D	protein	323	Homo sapiens	Q9NWZ3 (AlphaFold model)

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

>8W3W_1 Interleukin-1 receptor-associated kinase 4 (chains A, B, C, D)
MHHHHHHGGENLYFQGENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGF
GVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDD
LCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANI
LLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVL
LEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCL
HEKKNKRPDIKKVQQLLQEMTAS

Ligands and cofactors

ID	Name	Formula	Copies
A1AFO	7-methoxy-1-{[(2S)-5-oxopyrrolidin-2-yl]methoxy}isoquinoline-6-carboxamide	C16 H17 N3 O4	4

Primary citation

In Retrospect: Root-Cause Analysis of Structure-Activity Relationships in IRAK4 Inhibitor Zimlovisertib (PF-06650833). Wright, S.W., Farley, K.A., Han, S. et al. ACS Med Chem Lett (2024) 15:540-545. DOI 10.1021/acsmedchemlett.4c00036 · PubMed

Other PDB entries of the same protein (UniProt Q9NWZ3 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6EGE 1.4 Å, Crystal structure of the unphosphorylated IRAK4 kinase domain Bound to a type I inhibitor
9NA5 1.73 Å, IRAK4 in Complex with Compound 24
6UYA 1.74 Å, Crystal structure of Compound 19 bound to IRAK4
8W3X 1.76 Å, Crystal structure of IRAK4 in complex with compound 6
6O95 1.77 Å, Structure of the IRAK4 kinase domain with compound 41
6O8U 1.8 Å, Crystal structure of IRAK4 in complex with compound 23
8UCC 1.8 Å, IRAK4 in complex with compound 20
5UIT 1.84 Å, Crystal structure of IRAK4 in complex with compound 14
8UCB 1.85 Å, IRAK4 in complex with compound 8
9R9K 1.87 Å, IRAK4 in complex with inhibitor
9R9G 1.88 Å, IRAK4 in complex with inhibitor
8SCE 1.89 Å, Crystal structure of IRAK4-HSA complexed with N-[(2R)-2-FLUORO-3-HYDROXY-3-METHYLBUTYL]-6…

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