PDB-9z4x: MENIN IN COMPLEX WITH JNJ-75276617 (Bleximenib)

ID or keywords:

Entry

Database: PDB / ID: 9z4x

Title

MENIN IN COMPLEX WITH JNJ-75276617 (Bleximenib)

Components

Menin

Keywords

TRANSCRIPTION/INHIBITOR / MENIN / MEN1 / MLL / TRANSCRIPTION / INHIBITOR COMPLEX / Bleximenib / TRANSCRIPTION-INHIBITOR complex

Function / homology

Function and homology information

negative regulation of cyclin-dependent protein serine/threonine kinase activity / Y-form DNA binding / MLL1/2 complex / osteoblast development / negative regulation of JNK cascade / T-helper 2 cell differentiation / Formation of WDR5-containing histone-modifying complexes / positive regulation of transforming growth factor beta receptor signaling pathway / negative regulation of protein phosphorylation / histone methyltransferase complex ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.95 Å

Authors

Shaffer, P.L.

Funding support

1items

Citation

Journal: Blood / Year: 2024
Title: Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias.
Authors: Kwon, M.C. / Thuring, J.W. / Querolle, O. / Dai, X. / Verhulst, T. / Pande, V. / Marien, A. / Goffin, D. / Wenge, D.V. / Yue, H. / Cutler, J.A. / Jin, C. / Perner, F. / Hogeling, S.M. / ...

History

Deposition	Nov 11, 2025	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Nov 26, 2025	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	9z4x.cif.gz	777.9 KB	Display	PDBx/mmCIF format
PDB format	pdb9z4x.ent.gz	648.6 KB	Display	PDB format
PDBx/mmJSON format	9z4x.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	9z4x_validation.pdf.gz	2.2 MB	Display	wwPDB validaton report
Full document	9z4x_full_validation.pdf.gz	2.2 MB	Display
Data in XML	9z4x_validation.xml.gz	74.7 KB	Display
Data in CIF	9z4x_validation.cif.gz	96.1 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/z4/9z4x ftp://data.pdbj.org/pub/pdb/validation_reports/z4/9z4x	HTTPS FTP

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Related structure data

Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#60 - Dec 2004 Ubiquitin similarity (1) #245 - May 2020 Spliceosomes similarity (1) #44 - Aug 2003 Calmodulin similarity (1) #234 - Jun 2019 MDM2 and Cancer similarity (2) #196 - Apr 2016 Lead Poisoning similarity (1) #28 - Apr 2002 Anthrax Toxin similarity (1) #112 - Apr 2009 Oct and Sox Transcription Factors similarity (1) #252 - Dec 2020 Hepatitis C Virus Protease/Helicase similarity (1) #9 - Sep 2000 Lysozyme similarity (1)

PDB pages

PDBj /

wwPDB /

NCBI

Related items in Molecule of the Month

#60 - Dec 2004
Ubiquitin
similarity (1)
#245 - May 2020
Spliceosomes
similarity (1)
#44 - Aug 2003
Calmodulin
similarity (1)
#234 - Jun 2019
MDM2 and Cancer
similarity (2)
#196 - Apr 2016
Lead Poisoning
similarity (1)
#28 - Apr 2002
Anthrax Toxin
similarity (1)
#112 - Apr 2009
Oct and Sox Transcription Factors
similarity (1)
#252 - Dec 2020
Hepatitis C Virus Protease/Helicase
similarity (1)
#9 - Sep 2000
Lysozyme
similarity (1)

Deposited unit

A: Menin

B: Menin

C: Menin

D: Menin

hetero molecules

242 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Menin

hetero molecules

defined by author
60.7 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Menin

hetero molecules

defined by author
60.7 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

3

C: Menin

hetero molecules

defined by author
60.4 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

4

D: Menin

hetero molecules

defined by author
60.4 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	143.372, 70.486, 145.561
Angle α, β, γ (deg.)	90.00, 91.68, 90.00
Int Tables number	4
Space group name H-M	P12₁1

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Protein , 1 types, 4 molecules ABCD

#1: Protein	Menin Mass: 59789.973 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MEN1, SCG2 / Production host: Escherichia coli (E. coli) / References: UniProt: O00255

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Non-polymers , 6 types, 98 molecules

#2: Chemical	ChemComp-BME / BETA-MERCAPTOETHANOL Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂H₆OS
#3: Chemical	ChemComp-9N6 / N-ethyl-5-fluoro-2-{[5-(2-{(3R)-6-[(2-methoxyethyl)(methyl)amino]-2-methylhexan-3-yl}-2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl]oxy}-N-(propan-2-yl)benzamide Mass: 599.783 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₃₂H₅₀FN₇O₃
#4: Chemical	ChemComp-NA / SODIUM ION Mass: 22.990 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Na / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃H₈O₃
#6: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO₄
#7: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 84 / Source method: isolated from a natural source / Formula: H₂O

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Details

Has ligand of interest	Y
Has protein modification	N

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 3.14 Å³/Da / Density % sol: 60.8 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion / Details: 100 mM Tris pH 6.75 , 5 M NaCl , 0.2 M MgCl2

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.9796 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 11, 2020
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9796 Å / Relative weight: 1
Reflection	Resolution: 2.95→145.5 Å / Num. obs: 40857 / % possible obs: 89.9 % / Redundancy: 3.8 % / R_rim(I) all: 0.185 / R_sym value: 0.16 / Net I/σ(I): 6.9
Reflection shell	Resolution: 2.96→3.2 Å / Redundancy: 3.5 % / Mean I/σ(I) obs: 1.4 / Num. unique obs: 2044 / R_rim(I) all: 0.998 / R_sym value: 0.849 / % possible all: 51.2

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Processing

Software

Name	Version	Classification
autoPROC		data reduction
XDS	(VERSION Jan 26	data reduction
autoPROC	(Version 1.1.7)	data scaling
Aimless		data scaling
REFMAC	5.8.0049	refinement
PDB_EXTRACT		data extraction
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.95→145.5 Å / Cor.coef. F_o:F_c: 0.91 / Cor.coef. F_o:F_c free: 0.837 / SU ML: 0.508 / Cross valid method: THROUGHOUT / ESU R Free: 0.633 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.29695	2014	4.9 %	RANDOM
R_work	0.23333	-	-	-
obs	0.23659	38841	89.9 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-1.77 Å²	0 Å²	-0.95 Å²
2-	-	2.45 Å²	0 Å²
3-	-	-	-0.63 Å²

Refinement step

Cycle: LAST / Resolution: 2.95→145.5 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	15264	0	199	84	15547

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.007	0.019	15184
X-RAY DIFFRACTION	r_bond_other_d	0.002	0.02	14099
X-RAY DIFFRACTION	r_angle_refined_deg	1.097	1.967	20681
X-RAY DIFFRACTION	r_angle_other_deg	0.889	3	32150
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.485	5	1921
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	34.126	23.602	633
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.882	15.124	2260
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	12.171	15	84
X-RAY DIFFRACTION	r_chiral_restr	0.053	0.2	2320
X-RAY DIFFRACTION	r_gen_planes_refined	0.004	0.021	17294
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	3484
X-RAY DIFFRACTION	r_mcbond_it	3.543	7.205	7729
X-RAY DIFFRACTION	r_mcbond_other	3.543	7.205	7728
X-RAY DIFFRACTION	r_mcangle_it	5.799	12.139	9635
X-RAY DIFFRACTION	r_mcangle_other	5.798	12.139	9636
X-RAY DIFFRACTION	r_scbond_it	3.352	7.491	7455
X-RAY DIFFRACTION	r_scbond_other	3.35	7.491	7451
X-RAY DIFFRACTION	r_scangle_other	5.483	12.537	11033
X-RAY DIFFRACTION	r_long_range_B_refined	7.999	32.026	16723
X-RAY DIFFRACTION	r_long_range_B_other	7.998	32.026	16721

LS refinement shell

Resolution: 2.955→3.031 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.369	3	-
R_work	0.275	118	-
obs	-	-	2.69 %

Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

ID	L11 (°²)	L12 (°²)	L13 (°²)	L22 (°²)	L23 (°²)	L33 (°²)	S11 (Å °)	S12 (Å °)	S13 (Å °)	S21 (Å °)	S22 (Å °)	S23 (Å °)	S31 (Å °)	S32 (Å °)	S33 (Å °)	T11 (Å²)	T12 (Å²)	T13 (Å²)	T22 (Å²)	T23 (Å²)	T33 (Å²)	Origin x (Å)	Origin y (Å)	Origin z (Å)
1	2.021	1.497	0.4646	5.3044	1.1929	2.412	0.0297	-0.2873	-0.0609	0.2069	0.081	0.0569	0.1874	0.0296	-0.1108	0.1128	0.0333	0.0084	0.0766	0.0467	0.1082	59.682	5.19	33.279
2	4.4297	-1.0008	1.8828	4.7542	0.3778	3.2416	-0.0629	-0.18	-0.7236	0.3651	0.0476	0.2696	0.3688	-0.2961	0.0153	0.2862	0.0349	0.0655	0.0994	0.0384	0.1877	45.277	-7.199	19.454
3	4.1586	0.8381	0.8888	0.2275	0.5035	2.2675	-0.0509	0.1792	0.4292	-0.0745	0.0115	0.0887	-0.291	-0.1697	0.0394	0.2674	0.0835	0.0866	0.0705	0.0851	0.1371	46.353	13.635	15.493
4	4.3339	-0.6977	0.9026	2.4872	1.3971	2.4834	-0.0768	0.1998	0.3699	-0.201	-0.0087	0.5311	-0.3474	-0.5121	0.0854	0.3836	0.1387	0.076	0.3089	0.1413	0.4019	19.945	12.518	9.993
5	2.9513	-1.1729	-0.0737	3.2355	-0.9613	1.9383	-0.0892	0.1563	0.1926	-0.0207	0.0672	-0.0953	-0.141	0.2335	0.022	0.1543	-0.0162	0.0475	0.0765	0.0507	0.1414	25.216	3.04	48.137
6	6.8864	-0.1796	1.2521	5.8711	1.7671	5.8492	-0.1276	0.5836	0.2289	-0.4293	0.3793	-0.3685	-0.5708	0.3081	-0.2518	0.2292	0.0058	0.1027	0.1023	0.0436	0.1767	4.861	13.701	42.812
7	3.3505	-0.5295	0.4275	1.669	-0.8482	1.6795	0.2364	0.0017	-0.4768	-0.1567	-0.3026	0.2633	0.2119	-0.1225	0.0663	0.2039	0.0146	0.0743	0.1193	-0.0729	0.1897	3.862	-7.482	45.458
8	3.0645	-0.9798	0.5031	2.3192	0.2686	1.9201	0.2121	0.5801	-0.5541	-0.8811	-0.1764	0.3751	0.1517	-0.2976	-0.0358	0.5741	0.1182	-0.0383	0.4951	-0.2495	0.3955	-14.111	-7.531	25.462
9	2.7736	0.3435	-0.1394	3.6648	-1.3281	3.2761	0.0585	-0.3302	0.0787	0.1253	0.0241	-0.0478	-0.1444	0.0586	-0.0825	0.1455	-0.036	0.0416	0.0501	-0.0276	0.0408	22.151	-15.268	98.277
10	0.8567	-0.3897	-2.1039	4.2692	0.7538	6.0849	-0.0483	-0.1383	0.1088	0.3612	-0.1327	-0.4766	-0.1503	0.503	0.181	0.2612	-0.053	-0.0867	0.0661	0.0728	0.2927	29.584	-3.748	79.076
11	1.6773	0.2181	0.3871	0.3228	-0.5428	3.3966	0.0541	0.2273	-0.4069	-0.1141	-0.0565	-0.1854	0.4969	-0.0015	0.0025	0.1925	0.0279	-0.0103	0.0829	-0.0062	0.1968	26.745	-24.572	76.619
12	3.1423	-2.1148	-0.8503	2.5414	-0.6574	1.9139	0.0954	-0.3486	0.2849	-0.3291	-0.0782	-0.6351	0.3134	0.82	-0.0172	0.378	0.1922	0.1478	0.7398	-0.31	0.8124	48.055	-23.747	60.111
13	2.9332	-0.7481	-0.7693	3.9479	1.6758	3.4743	-0.0569	-0.1912	-0.2465	-0.1333	0.1693	0.4218	0.0464	-0.5058	-0.1123	0.1534	-0.0635	0.0554	0.1642	0.0767	0.1323	32.51	-14.617	134.82
14	7.7137	1.406	0.5358	2.378	-0.5467	3.552	-0.2564	0.1887	-0.6816	-0.2709	0.2346	0.173	0.7371	-0.0751	0.0219	0.2686	-0.0332	0.0952	0.0244	0.0175	0.2457	49.424	-23.978	121.398
15	2.5281	0.3293	-1.5309	0.5856	0.6425	3.1466	0.0831	0.0584	0.5232	-0.1062	0.0546	0.018	-0.5055	0.2122	-0.1377	0.1768	-0.0576	-0.0127	0.0389	0.0584	0.2048	50.447	-3.052	123.959
16	3.4244	-0.4067	-1.4442	3.4629	-0.7355	2.7296	0.0577	0.5072	0.3483	-0.5826	-0.1192	-0.1021	-0.152	-0.0701	0.0616	0.3604	-0.1	-0.0311	0.1755	0.0897	0.2457	59.239	-1.945	98.37

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	2 - 170
2	X-RAY DIFFRACTION	2	A	171 - 229
3	X-RAY DIFFRACTION	3	A	230 - 354
4	X-RAY DIFFRACTION	4	A	355 - 459
5	X-RAY DIFFRACTION	4	A	548 - 582
6	X-RAY DIFFRACTION	4	A	701
7	X-RAY DIFFRACTION	5	B	2 - 170
8	X-RAY DIFFRACTION	6	B	171 - 229
9	X-RAY DIFFRACTION	7	B	230 - 354
10	X-RAY DIFFRACTION	8	B	355 - 459
11	X-RAY DIFFRACTION	8	B	548 - 582
12	X-RAY DIFFRACTION	8	B	701
13	X-RAY DIFFRACTION	9	C	2 - 170
14	X-RAY DIFFRACTION	10	C	171 - 229
15	X-RAY DIFFRACTION	11	C	230 - 354
16	X-RAY DIFFRACTION	12	C	355 - 459
17	X-RAY DIFFRACTION	12	C	548 - 582
18	X-RAY DIFFRACTION	13	D	2 - 170
19	X-RAY DIFFRACTION	14	D	171 - 229
20	X-RAY DIFFRACTION	15	D	230 - 354
21	X-RAY DIFFRACTION	16	D	355 - 459
22	X-RAY DIFFRACTION	16	D	547 - 582

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