PDB-9y8n: Crystal structure of the Kelch domain of human KLHL12 with compound 8m

ID or keywords:

Entry

Database: PDB / ID: 9y8n

Title

Crystal structure of the Kelch domain of human KLHL12 with compound 8m

Components

Kelch-like protein 12

Keywords

LIGASE / E3 ligase / fragment-based drug discovery / PROTAC

Function / homology

Function and homology information

neural crest formation / neural crest cell development / COPII vesicle coat assembly / COPII vesicle coat / COPII-coated ER to Golgi transport vesicle / Cul3-RING ubiquitin ligase complex / endoplasmic reticulum to Golgi vesicle-mediated transport / protein monoubiquitination / ubiquitin-like ligase-substrate adaptor activity / Degradation of DVL ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.308 Å

Authors

Amporndanai, K. / Madrigal-Carrillo, E.A. / Rietz, T.A. / Zhao, B. / Fesik, S.W.

Funding support

United States, 1items

Citation

Journal: J.Med.Chem. / Year: 2026
Title: Identification of KLHL12 Ligands Using Fragment-Based Methods.
Authors: Waterson, A.G. / Vadukoot, A. / Jana, S. / Cui, J. / Luong, K. / Rietz, T.A. / Madrigal-Carrillo, E.A. / Lehmann, B.D. / Sensintaffar, J.L. / Zhao, B. / Amporndanai, K. / Petros, Z.A. / ...

History

Deposition	Sep 11, 2025	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Apr 8, 2026	Provider: repository / Type: Initial release
Revision 1.1	Apr 22, 2026	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	9y8n.cif.gz	288.3 KB	Display	PDBx/mmCIF format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/y8/9y8n ftp://data.pdbj.org/pub/pdb/validation_reports/y8/9y8n	HTTPS FTP

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Related structure data

Related structure data	9y8jC 9y8kC 9y8lC 9y8mC 9y8oC 9y8qC 9y8rC 9y8sC 9y8tC 9y8uC 9y8vC C: citing same article (ref.)
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 (2) #110 - Feb 2009 Auxin and TIR1 Ubiquitin Ligase similarity (1) #240 - Dec 2019 Hypoxia-Inducible Factors similarity (1) #218 - Feb 2018 EPSP Synthase and Weedkillers similarity (1) #172 - Apr 2014 RecA and Rad51 similarity (1) #234 - Jun 2019 MDM2 and Cancer similarity (1)

Deposited unit

A: Kelch-like protein 12

hetero molecules

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

1

Idetical with deposited unit
defined by author&software
Evidence: gel filtration

Unit cell

Length a, b, c (Å)	79.633, 79.633, 74.382
Angle α, β, γ (deg.)	90, 90, 90
Int Tables number	92
Space group name H-M	P4₁2₁2

Components on special symmetry positions

ID	Model	Components
1	1	A-891- HOH
2	1	A-978- HOH
3	1	A-990- HOH
4	1	A-1003- HOH

#1: Protein	Kelch-like protein 12 / CUL3-interacting protein 1 / DKIR homolog / hDKIR Mass: 32148.941 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KLHL12, C3IP1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q53G59
#2: Chemical	ChemComp-A1CTL / 2-(4-methyl-1H-imidazo[4,5-c]pyridin-1-yl)-N-(2,4,6-trichlorophenyl)acetamide Mass: 369.633 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₅H₁₁Cl₃N₄O / Feature type: SUBJECT OF INVESTIGATION
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 308 / Source method: isolated from a natural source / Formula: H₂O
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: 1.83 Å³/Da / Density % sol: 32.93 %
Crystal grow	Temperature: 291 K / Method: vapor diffusion, hanging drop / Details: 0.1M Bis-Tris pH 5.5, 0.2M MgCl2 and 25% PEG3350

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 0.99 Å
Detector	Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Mar 2, 2022
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.99 Å / Relative weight: 1
Reflection	Resolution: 1.308→33.72 Å / Num. obs: 45864 / % possible obs: 99.2 % / Redundancy: 11.4 % / CC_1/2: 0.997 / R_merge(I) obs: 0.132 / Net I/σ(I): 8.4
Reflection shell	Resolution: 1.308→1.33 Å / Redundancy: 10.7 % / R_merge(I) obs: 0.561 / Mean I/σ(I) obs: 1 / Num. unique obs: 5505 / CC_1/2: 0.382 / % possible all: 78.6

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0425	refinement
MOSFLM		data reduction
Aimless		data scaling
MOLREP		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.308→33.72 Å / Cor.coef. F_o:F_c: 0.968 / Cor.coef. F_o:F_c free: 0.952 / SU B: 3.145 / SU ML: 0.054 / Cross valid method: FREE R-VALUE / ESU R: 0.08 / ESU R Free: 0.071
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2038	2280	4.971 %
R_work	0.1586	43584	-
all	0.161	-	-
obs	-	45864	78.749 %

Solvent computation

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

Displacement parameters

B_iso mean: 14.441 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.497 Å²	0 Å²	0 Å²
2-	-	0.497 Å²	0 Å²
3-	-	-	-0.993 Å²

Refinement step

Cycle: LAST / Resolution: 1.308→33.72 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2186	0	23	308	2517

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.012	0.012	2282
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	2071
X-RAY DIFFRACTION	r_angle_refined_deg	1.907	1.806	3118
X-RAY DIFFRACTION	r_angle_other_deg	0.703	1.744	4754
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.721	5	298
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	10.66	5	18
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.09	10	350
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	17.293	10	96
X-RAY DIFFRACTION	r_chiral_restr	0.102	0.2	347
X-RAY DIFFRACTION	r_gen_planes_refined	0.011	0.02	2781
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	543
X-RAY DIFFRACTION	r_nbd_refined	0.208	0.2	350
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.189	0.2	1982
X-RAY DIFFRACTION	r_nbtor_refined	0.175	0.2	1107
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.086	0.2	1203
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.269	0.2	203
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.182	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.234	0.2	23
X-RAY DIFFRACTION	r_nbd_other	0.228	0.2	87
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.337	0.2	49
X-RAY DIFFRACTION	r_mcbond_it	2.637	0.847	1159
X-RAY DIFFRACTION	r_mcbond_other	2.611	0.846	1159
X-RAY DIFFRACTION	r_mcangle_it	3.895	1.525	1450
X-RAY DIFFRACTION	r_mcangle_other	3.901	1.526	1451
X-RAY DIFFRACTION	r_scbond_it	3.577	1.002	1123
X-RAY DIFFRACTION	r_scbond_other	3.576	1.002	1124
X-RAY DIFFRACTION	r_scangle_it	5.152	1.776	1662
X-RAY DIFFRACTION	r_scangle_other	5.15	1.776	1663
X-RAY DIFFRACTION	r_lrange_it	9.802	12.236	10193
X-RAY DIFFRACTION	r_lrange_other	8.007	11.348	9847
X-RAY DIFFRACTION	r_rigid_bond_restr	3.925	3	4353

LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	R_factor all	Num. reflection all	Fsc free	Fsc work	% reflection obs (%)	WR_factor R_work
1.308-1.342	0.199	4	0.206	28	0.205	4246	0.976	0.964	0.7537	0.222
1.342-1.378	0.382	18	0.258	261	0.265	4134	0.892	0.949	6.7489	0.265
1.378-1.418	0.317	47	0.273	1132	0.275	4009	0.936	0.944	29.4088	0.278
1.418-1.462	0.264	136	0.264	2476	0.264	3895	0.95	0.945	67.0603	0.266
1.462-1.51	0.26	163	0.23	3458	0.231	3799	0.939	0.959	95.3146	0.231
1.51-1.563	0.231	212	0.173	3468	0.176	3683	0.96	0.979	99.9185	0.171
1.563-1.621	0.208	207	0.152	3344	0.155	3551	0.97	0.985	100	0.146
1.621-1.687	0.212	136	0.14	3265	0.143	3401	0.972	0.987	100	0.131
1.687-1.762	0.242	151	0.14	3153	0.144	3304	0.959	0.987	100	0.128
1.762-1.848	0.186	154	0.141	2999	0.143	3154	0.977	0.987	99.9683	0.131
1.848-1.948	0.2	146	0.148	2853	0.15	2999	0.973	0.985	100	0.141
1.948-2.065	0.239	143	0.145	2694	0.15	2840	0.963	0.985	99.8944	0.142
2.065-2.207	0.175	127	0.146	2557	0.148	2684	0.981	0.986	100	0.147
2.207-2.383	0.19	125	0.151	2387	0.153	2514	0.975	0.985	99.9204	0.154
2.383-2.61	0.223	99	0.152	2231	0.156	2330	0.965	0.984	100	0.158
2.61-2.915	0.174	93	0.157	2016	0.158	2109	0.982	0.983	100	0.17
2.915-3.362	0.19	130	0.155	1762	0.157	1892	0.978	0.982	100	0.174
3.362-4.108	0.19	84	0.152	1528	0.154	1612	0.976	0.984	100	0.177
4.108-5.767	0.166	71	0.152	1217	0.153	1289	0.983	0.984	99.9224	0.186
5.767-33.72	0.29	34	0.202	755	0.205	790	0.944	0.97	99.8734	0.242

Refinement TLS params.

Method: refined / Origin x: -16.9708 Å / Origin y: 14.8388 Å / Origin z: -0.2468 Å

	11	12	13	21	22	23	31	32	33
T	0.0176 Å²	-0.0031 Å²	0.0046 Å²	-	0.0107 Å²	-0.0018 Å²	-	-	0.0033 Å²
L	1.0392 °²	-0.0708 °²	0.0369 °²	-	0.7775 °²	0.0066 °²	-	-	0.4037 °²
S	0.0054 Å °	0.0827 Å °	0.01 Å °	-0.0994 Å °	0.005 Å °	-0.0065 Å °	-0.0252 Å °	-0.0158 Å °	-0.0104 Å °

Refinement TLS group

Selection: ALL

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