PDB-9xyl: Human prolyl endopeptidase (PREP) - complex with S17092

ID or keywords:

Entry

Database: PDB / ID: 9xyl

Title

Human prolyl endopeptidase (PREP) - complex with S17092

Components

Prolyl endopeptidase

Keywords

HYDROLASE / inhibitor-bound / peptide cleavage

Function / homology

Function and homology information

prolyl oligopeptidase / oligopeptidase activity / angiotensin maturation / metallocarboxypeptidase activity / serine-type peptidase activity / serine-type endopeptidase activity / proteolysis / extracellular region / nucleus / membrane ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.81 Å

Authors

Fucci, I.J. / Yoo, E. / Monteiro, D.C.F.

Funding support

United States, 1items

Citation

Journal: J.Med.Chem. / Year: 2026
Title: Structure-Guided Optimization of 4-Chloro-Pyrazolopyridine Analogs for Covalent PREP Inhibition.
Authors: Thakur, K. / Fucci, I. / Pandian, J. / Suazo, K.F. / Monteiro, D.C.F. / Yoo, E.

History

Deposition	Aug 26, 2025	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Jan 21, 2026	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	9xyl.cif.gz	3.8 MB	Display	PDBx/mmCIF format
PDB format	pdb9xyl.ent.gz		Display	PDB format
PDBx/mmJSON format	9xyl.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

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

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Related structure data

Related structure data	9q5gC 9q5xC 9q5yC 9q5zC 9q62C 9q64C 9q65C 9q66C 9q6jC 9q6kC 9q6lC 9q6xC 9xykC 9xzzC C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search
Experimental dataset #1	Data reference: 10.15785/SBGRID/1215 / Data set type: diffraction image data

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#202 - Oct 2016 Dipeptidyl Peptidase 4 similarity (4) #190 - Oct 2015 Two-component Systems similarity (1)

Deposited unit

A: Prolyl endopeptidase

B: Prolyl endopeptidase

C: Prolyl endopeptidase

D: Prolyl endopeptidase

E: Prolyl endopeptidase

F: Prolyl endopeptidase

hetero molecules

489 kDa, 6 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Prolyl endopeptidase

hetero molecules

defined by author
Evidence: gel filtration
81.8 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Prolyl endopeptidase

hetero molecules

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

3

C: Prolyl endopeptidase

hetero molecules

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

4

D: Prolyl endopeptidase

hetero molecules

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

5

E: Prolyl endopeptidase

hetero molecules

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

6

F: Prolyl endopeptidase

hetero molecules

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

Unit cell

Length a, b, c (Å)	67.187, 105.735, 155.67
Angle α, β, γ (deg.)	81.782, 89.794, 89.701
Int Tables number	1
Space group name H-M	P1

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Protein , 1 types, 6 molecules ABCDEF

#1: Protein	Prolyl endopeptidase / PE / Post-proline cleaving enzyme Mass: 80851.367 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PREP, PEP / Production host: Escherichia coli (E. coli) / References: UniProt: P48147, prolyl oligopeptidase

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Non-polymers , 6 types, 1774 molecules

#2: Chemical	ChemComp-A1CRK / {(2S,3aS,7aS)-1-[(1R,2R)-2-phenylcyclopropane-1-carbonyl]octahydro-1H-indol-2-yl}(1,3-thiazolidin-3-yl)methanone Mass: 384.535 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C₂₂H₂₈N₂O₂S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C₃H₈O₃
#4: Chemical	ChemComp-SCN / THIOCYANATE ION Mass: 58.082 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: CNS
#5: Chemical	ChemComp-PEG / DI(HYDROXYETHYL)ETHER Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₄H₁₀O₃
#6: Chemical	ChemComp-B3P / 2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL Mass: 282.334 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₁H₂₆N₂O₆ / Comment: pH buffer*YM
#7: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 1747 / 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: 2.26 Å³/Da / Density % sol: 45.48 %
Crystal grow	Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 25-30% PEG 3350, 200 mM KSCN and 100 mM bis-tris propane pH 7.5

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-1 / Wavelength: 0.9201 Å
Detector	Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: May 25, 2024
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9201 Å / Relative weight: 1
Reflection	Resolution: 1.81→29.68 Å / Num. obs: 286151 / % possible obs: 83.3 % / Redundancy: 1.8 % / B_iso Wilson estimate: 22.5 Å² / CC_1/2: 0.99 / R_merge(I) obs: 0.07 / R_pim(I) all: 0.07 / R_rim(I) all: 0.1 / Net I/σ(I): 5.2
Reflection shell	Resolution: 1.81→1.93 Å / Redundancy: 1.8 % / R_merge(I) obs: 0.371 / Num. unique obs: 14310 / CC_1/2: 0.62 / R_pim(I) all: 0.371 / R_rim(I) all: 0.524 / % possible all: 53.3

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0430 (refmacat 0.4.100)	refinement
autoPROC		data reduction
autoPROC		data scaling
MOLREP		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.81→29.68 Å / Cor.coef. F_o:F_c: 0.947 / Cor.coef. F_o:F_c free: 0.907 / SU B: 9.379 / SU ML: 0.142 / Cross valid method: FREE R-VALUE / ESU R: 0.207 / ESU R Free: 0.185
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2489	14477	5.059 %
R_work	0.1907	271673	-
all	0.194	-	-
obs	-	286150	74.078 %

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: 25.592 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.329 Å²	0.078 Å²	0.185 Å²
2-	-	-0.566 Å²	0.008 Å²
3-	-	-	0.231 Å²

Refinement step

Cycle: LAST / Resolution: 1.81→29.68 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	34038	0	281	1747	36066

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.016	0.012	35262
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	32317
X-RAY DIFFRACTION	r_angle_refined_deg	2.617	1.819	47803
X-RAY DIFFRACTION	r_angle_other_deg	0.866	1.762	74698
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	8.065	5	4244
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	13.757	7	180
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	15.82	10	5823
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	15.504	10	1700
X-RAY DIFFRACTION	r_chiral_restr	0.124	0.2	5064
X-RAY DIFFRACTION	r_gen_planes_refined	0.014	0.02	41306
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	8230
X-RAY DIFFRACTION	r_nbd_refined	0.22	0.2	6909
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.211	0.2	31634
X-RAY DIFFRACTION	r_nbtor_refined	0.197	0.2	16888
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.097	0.2	18708
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.194	0.2	1859
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.111	0.2	21
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.244	0.2	60
X-RAY DIFFRACTION	r_nbd_other	0.258	0.2	252
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.266	0.2	39
X-RAY DIFFRACTION	r_mcbond_it	1.794	1.435	16980
X-RAY DIFFRACTION	r_mcbond_other	1.787	1.434	16973
X-RAY DIFFRACTION	r_mcangle_it	2.49	2.57	21209
X-RAY DIFFRACTION	r_mcangle_other	2.49	2.571	21210
X-RAY DIFFRACTION	r_scbond_it	2.518	1.672	18282
X-RAY DIFFRACTION	r_scbond_other	2.517	1.672	18283
X-RAY DIFFRACTION	r_scangle_it	3.676	2.962	26573
X-RAY DIFFRACTION	r_scangle_other	3.676	2.962	26574
X-RAY DIFFRACTION	r_lrange_it	4.884	16.392	39337
X-RAY DIFFRACTION	r_lrange_other	4.864	16.202	39119

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
1.81-1.857	0.272	103	0.218	1870	X-RAY DIFFRACTION	6.9172
1.857-1.908	0.284	356	0.249	6939	X-RAY DIFFRACTION	26.3091
1.908-1.963	0.298	740	0.248	14228	X-RAY DIFFRACTION	55.3817
1.963-2.023	0.298	1101	0.245	19642	X-RAY DIFFRACTION	79.024
2.023-2.089	0.284	1145	0.229	21282	X-RAY DIFFRACTION	88.3927
2.089-2.162	0.269	1185	0.219	21273	X-RAY DIFFRACTION	90.9341
2.162-2.243	0.289	1109	0.221	20470	X-RAY DIFFRACTION	91.0314
2.243-2.334	0.27	1029	0.213	19757	X-RAY DIFFRACTION	91.4756
2.334-2.438	0.27	952	0.2	19013	X-RAY DIFFRACTION	90.9816
2.438-2.556	0.287	933	0.205	17660	X-RAY DIFFRACTION	88.7918
2.556-2.693	0.282	859	0.198	16609	X-RAY DIFFRACTION	87.3968
2.693-2.855	0.248	781	0.181	15343	X-RAY DIFFRACTION	85.5884
2.855-3.05	0.267	773	0.184	14325	X-RAY DIFFRACTION	85.0639
3.05-3.291	0.238	754	0.175	12861	X-RAY DIFFRACTION	82.5302
3.291-3.601	0.222	659	0.173	11378	X-RAY DIFFRACTION	79.1127
3.601-4.019	0.213	521	0.163	10432	X-RAY DIFFRACTION	79.6814
4.019-4.626	0.196	466	0.153	9307	X-RAY DIFFRACTION	80.2118
4.626-5.632	0.216	457	0.166	8194	X-RAY DIFFRACTION	83.7221
5.632-7.825	0.244	320	0.199	6896	X-RAY DIFFRACTION	89.7959
7.825-29.68	0.21	234	0.18	4194	X-RAY DIFFRACTION	94.2529

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	0.6216	-0.0273	0.2058	0.3483	0.0602	0.4523	0.0154	0.0065	0.0323	-0.0639	0.0065	0.0137	0.0015	-0.0111	-0.0219	0.0125	-0.0052	-0.0057	0.067	0.0106	0.0355	0.6514	-0.1611	-0.3377
2	0.534	-0.2654	-0.0443	0.7564	0.0408	0.3199	0.0095	0.0182	-0.0317	-0.0046	-0.0347	-0.0178	0.0248	0.0266	0.0252	0.0046	-0.002	-0.002	0.0855	0.0039	0.0105	-31.9251	52.5039	5.126
3	0.4212	0.1644	0.0893	0.5751	0.1527	0.4566	0.0212	-0.0073	0.0416	-0.0013	0.0028	-0.057	-0.0367	0.0211	-0.024	0.0215	-0.0014	-0.0033	0.0741	-0.0033	0.0437	1.4079	-31.7583	50.2846
4	0.6307	-0.1057	-0.2472	0.5518	0.1676	0.6562	-0.0131	-0.0448	-0.0655	0.0182	-0.0212	-0.0214	0.0328	0.0138	0.0344	0.0753	0.0039	-0.0258	0.0967	0.0072	0.0589	-28.5736	79.4939	-50.7561
5	0.6211	0.0287	0.1898	0.5582	0.2733	0.7493	0.0287	0.0542	0.0646	-0.0213	0.0009	-0.0001	-0.0207	-0.0143	-0.0295	0.078	-0.0051	0.0235	0.1157	0.0131	0.0588	4.7079	27.2557	-48.8103
6	0.5343	-0.0546	-0.1688	0.5351	0.1984	0.6058	-0.0081	-0.0654	-0.0486	0.0702	-0.0106	0.0162	0.0601	-0.009	0.0188	0.0307	-0.015	-0.0246	0.089	0.0053	0.0698	-32.9596	104.5043	-100.3639

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	ALL	Ap	5 - 711
2	X-RAY DIFFRACTION	2	ALL	Bp	5 - 711
3	X-RAY DIFFRACTION	3	ALL	Cp	5 - 711
4	X-RAY DIFFRACTION	4	ALL	Dp	5 - 711
5	X-RAY DIFFRACTION	5	ALL	Ep	5 - 711
6	X-RAY DIFFRACTION	6	ALL	Fp	5 - 711

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