PDB-9y8o: Crystal structure of the Kelch domain of human KLHL12 with compound 9c

ID or keywords:

Entry

Database: PDB / ID: 9y8o

Title

Crystal structure of the Kelch domain of human KLHL12 with compound 9c

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: 1.286 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	9y8o.cif.gz	278.1 KB	Display	PDBx/mmCIF format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/y8/9y8o ftp://data.pdbj.org/pub/pdb/validation_reports/y8/9y8o	HTTPS FTP

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Related structure data

Related structure data	9y8jC 9y8kC 9y8lC 9y8mC 9y8nC 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

32.6 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)	79.67, 79.67, 77.26
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-862- 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-A1CTM / 2-(2-amino-4-methyl-1H-1,3-benzimidazol-1-yl)-N-[2,6-dichloro-4-(phenoxyacetyl)phenyl]acetamide Mass: 483.347 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₄H₂₀Cl₂N₄O₃ / Feature type: SUBJECT OF INVESTIGATION
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 348 / 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: 1.91 Å³/Da / Density % sol: 35.49 %
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-G / Wavelength: 0.97857 Å
Detector	Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Sep 28, 2021
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97857 Å / Relative weight: 1
Reflection	Resolution: 1.286→55.53 Å / Num. obs: 63553 / % possible obs: 91.4 % / Redundancy: 12.8 % / CC_1/2: 0.999 / R_merge(I) obs: 0.09 / Net I/σ(I): 10.2
Reflection shell	Resolution: 1.286→1.31 Å / Redundancy: 12.9 % / R_merge(I) obs: 0.471 / Mean I/σ(I) obs: 4.2 / Num. unique obs: 6216 / CC_1/2: 0.98 / % possible all: 100

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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: 1.286→55.525 Å / Cor.coef. F_o:F_c: 0.973 / Cor.coef. F_o:F_c free: 0.966 / SU B: 1.39 / SU ML: 0.03 / Cross valid method: FREE R-VALUE / ESU R: 0.046 / ESU R Free: 0.048
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.1772	3122	4.912 %
R_work	0.1547	60431	-
all	0.156	-	-
obs	-	63553	99.958 %

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: 13.755 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.189 Å²	0 Å²	0 Å²
2-	-	0.189 Å²	0 Å²
3-	-	-	-0.377 Å²

Refinement step

Cycle: LAST / Resolution: 1.286→55.525 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2186	0	33	348	2567

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.012	0.012	2278
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	2048
X-RAY DIFFRACTION	r_angle_refined_deg	1.871	1.79	3106
X-RAY DIFFRACTION	r_angle_other_deg	0.671	1.737	4700
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	8.089	5	288
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	20.728	5.952	21
X-RAY DIFFRACTION	r_dihedral_angle_other_2_deg	1.572	10	1
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	10.324	10	344
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	16.266	10	97
X-RAY DIFFRACTION	r_chiral_restr	0.1	0.2	341
X-RAY DIFFRACTION	r_gen_planes_refined	0.01	0.02	2767
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	540
X-RAY DIFFRACTION	r_nbd_refined	0.216	0.2	398
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.186	0.2	2015
X-RAY DIFFRACTION	r_nbtor_refined	0.177	0.2	1128
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.088	0.2	1200
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.162	0.2	201
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.103	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.097	0.2	11
X-RAY DIFFRACTION	r_nbd_other	0.158	0.2	61
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.289	0.2	39
X-RAY DIFFRACTION	r_mcbond_it	0.983	0.71	1152
X-RAY DIFFRACTION	r_mcbond_other	0.978	0.71	1152
X-RAY DIFFRACTION	r_mcangle_it	1.564	1.274	1440
X-RAY DIFFRACTION	r_mcangle_other	1.563	1.275	1441
X-RAY DIFFRACTION	r_scbond_it	1.851	0.907	1126
X-RAY DIFFRACTION	r_scbond_other	1.851	0.907	1126
X-RAY DIFFRACTION	r_scangle_it	2.834	1.578	1666
X-RAY DIFFRACTION	r_scangle_other	2.833	1.578	1667
X-RAY DIFFRACTION	r_lrange_it	4.215	10.662	10524
X-RAY DIFFRACTION	r_lrange_other	3.893	9.607	10095

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
1.286-1.319	0.229	253	0.194	4364	0.196	4617	0.967	0.976	100	0.167
1.319-1.356	0.21	203	0.186	4326	0.187	4529	0.976	0.978	100	0.156
1.356-1.395	0.219	204	0.176	4188	0.178	4392	0.973	0.98	100	0.151
1.395-1.438	0.204	232	0.173	4036	0.175	4268	0.972	0.981	100	0.151
1.438-1.485	0.196	201	0.166	3932	0.168	4133	0.973	0.982	100	0.145
1.485-1.537	0.192	206	0.162	3826	0.163	4032	0.978	0.984	100	0.142
1.537-1.595	0.168	206	0.158	3661	0.158	3867	0.98	0.985	100	0.141
1.595-1.66	0.187	183	0.162	3555	0.163	3751	0.978	0.983	99.6534	0.147
1.66-1.734	0.189	176	0.162	3422	0.163	3599	0.979	0.983	99.9722	0.151
1.734-1.818	0.17	171	0.151	3272	0.152	3443	0.982	0.986	100	0.143
1.818-1.916	0.16	175	0.147	3093	0.148	3268	0.984	0.986	100	0.142
1.916-2.033	0.166	158	0.139	2949	0.14	3107	0.984	0.988	100	0.136
2.033-2.173	0.155	146	0.141	2795	0.142	2941	0.984	0.988	100	0.141
2.173-2.346	0.137	106	0.145	2642	0.145	2748	0.987	0.987	100	0.147
2.346-2.57	0.177	119	0.149	2414	0.151	2533	0.981	0.986	100	0.154
2.57-2.873	0.183	113	0.153	2177	0.154	2298	0.979	0.985	99.6519	0.161
2.873-3.315	0.185	104	0.152	1954	0.153	2059	0.98	0.985	99.9514	0.165
3.315-4.057	0.133	61	0.141	1698	0.141	1759	0.99	0.988	100	0.159
4.057-5.722	0.165	73	0.136	1324	0.137	1397	0.985	0.99	100	0.161
5.722-55.525	0.33	32	0.217	803	0.221	838	0.923	0.969	99.642	0.251

Refinement TLS params.

Method: refined / Origin x: -17.1958 Å / Origin y: 14.6319 Å / Origin z: 0.1828 Å

	11	12	13	21	22	23	31	32	33
T	0.0142 Å²	-0.0009 Å²	0.0104 Å²	-	0.0053 Å²	0.0005 Å²	-	-	0.0079 Å²
L	0.9791 °²	-0.211 °²	-0.1497 °²	-	1.3175 °²	0.202 °²	-	-	0.2458 °²
S	0.0229 Å °	0.0688 Å °	0.0322 Å °	-0.128 Å °	0.0105 Å °	-0.0899 Å °	-0.0389 Å °	-0.0065 Å °	-0.0334 Å °

Refinement TLS group

Selection: ALL

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