PDB-4pv7: Cocrystal structure of dipeptidyl-peptidase 4 with an indole scaf...

ID or keywords:

Entry

Database: PDB / ID: 4pv7

Title

Cocrystal structure of dipeptidyl-peptidase 4 with an indole scaffold inhibitor

Components

Dipeptidyl peptidase 4 soluble form

Keywords

HYDROLASE/HYDROLASE INHIBITOR /

Beta-Propeller /

Hydrolase / extrocellular side / HYDROLASE-HYDROLASE INHIBITOR complex

Function / homology

Function and homology information

glucagon processing / negative regulation of neutrophil chemotaxis / Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) / regulation of cell-cell adhesion mediated by integrin / negative regulation of extracellular matrix disassembly / psychomotor behavior /

dipeptidyl-peptidase IV /

chemorepellent activity / intercellular canaliculus / dipeptidyl-peptidase activity ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 3.24 Å

Authors

Xiao, P. / Guo, R. / Huang, S. / Cui, H. / Ye, S. / Zhang, Z.

Citation

Journal: Chin.Chem.Lett. / Year: 2014
Title: Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold
Authors: Xiao, P. / Guo, R. / Huang, S. / Cui, H. / Ye, S. / Zhang, Z.

History

Deposition	Mar 15, 2014	Deposition site: RCSB / Processing site: PDBJ
Revision 1.0	Mar 18, 2015	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	4pv7.cif.gz	608.4 KB	Display	PDBx/mmCIF format
PDB format	pdb4pv7.ent.gz	526.7 KB	Display	PDB format
PDBx/mmJSON format	4pv7.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/pv/4pv7 ftp://data.pdbj.org/pub/pdb/validation_reports/pv/4pv7	HTTPS FTP

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Related structure data

Similar structure data	2g5t-d 3oc0-d 2i78-1 5j3j-d 3o9v-3 2ajd-1 4dtc-d 2oag-2 5t4f-d 2g63-2 5kby-2 2gbg-d 3g0b-1 2bgr-d 2onc-1 5zid-d 2ajl-d 2rgu-d 4j3j-d 5y7k-1 Search similar-shape structures by Omokage search (details) 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	#202 - Oct 2016 Dipeptidyl Peptidase 4 similarity (10) #184 - Apr 2015 Glucagon similarity (1) #149 - May 2012 Leptin similarity (1)

Deposited unit

A: Dipeptidyl peptidase 4 soluble form

B: Dipeptidyl peptidase 4 soluble form

hetero molecules

175 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	79.815, 79.815, 286.756
Angle α, β, γ (deg.)	90.00, 90.00, 120.00
Int Tables number	145
Space group name H-M	P3₂

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	A
2	1	B

NCS domain segments:

Dom-ID	Component-ID	Ens-ID	Refine code	Auth asym-ID	Auth seq-ID
1	1	1	1	A	40 - 766
2	1	1	1	B	40 - 766
1	2	1	1	A	1000
2	2	1	1	B	1000

#1: Protein	Dipeptidyl peptidase 4 soluble form / ADABP / Adenosine deaminase complexing protein 2 / ADCP-2 / Dipeptidyl peptidase IV / DPP IV / T- ...ADABP / Adenosine deaminase complexing protein 2 / ADCP-2 / Dipeptidyl peptidase IV / DPP IV / T-cell activation antigen CD26 / TP103 / Dipeptidyl peptidase IV soluble form Mass: 87295.617 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ADCP2, CD26, DPP4 / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P27487, dipeptidyl-peptidase IV
#2: Chemical	ChemComp-CJP / 1-[2-(2,4-dichlorophenyl)-1-(methylsulfonyl)-1H-indol-3-yl]methanamine Mass: 369.266 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₆H₁₄Cl₂N₂O₂S

#1: Protein

Dipeptidyl peptidase 4 soluble form / ADABP / Adenosine deaminase complexing protein 2 / ADCP-2 / Dipeptidyl peptidase IV / DPP IV / T- ...

Mass: 87295.617 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Gene: ADCP2, CD26, DPP4 / Cell line (production host): SF9 / Production host:

SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P27487,

dipeptidyl-peptidase IV

#2: Chemical

ChemComp-CJP / 1-[2-(2,4-dichlorophenyl)-1-(methylsulfonyl)-1H-indol-3-yl]methanamine

Mass: 369.266 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₆H₁₄Cl₂N₂O₂S

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 3.02 Å³/Da / Density % sol: 59.28 %
Crystal grow	Temperature: 289 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 20% PEG MME 2000, 0.1M Bicine, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 289.0K

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.9791 Å
Detector	Type: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 21, 2013
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9791 Å / Relative weight: 1
Reflection	Resolution: 3.24→50 Å / Num. obs: 32631 / % possible obs: 99.9 % / Redundancy: 5.1 % / R_merge(I) obs: 0.11 / R_sym value: 0.11 / Net I/σ(I): 29
Reflection shell	Resolution: 3.24→3.31 Å / R_merge(I) obs: 1 / Mean I/σ(I) obs: 2 / R_sym value: 1 / % possible all: 100

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Processing

Software

Name	Version	Classification
HKL-2000		data collection
PHASES		phasing
REFMAC	5.2.0019	refinement
HKL-2000		data reduction
HKL-2000		data scaling

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 3.24→49.75 Å / Cor.coef. F_o:F_c: 0.933 / Cor.coef. F_o:F_c free: 0.887 / SU B: 59.906 / SU ML: 0.449 / Cross valid method: THROUGHOUT / ESU R Free: 0.536 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.26397	1332	4.1 %	RANDOM
R_work	0.22324	-	-	-
all	0.22494	31241	-	-
obs	0.22494	31241	100 %	-

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_iso mean: 146.734 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	4.88 Å²	2.44 Å²	0 Å²
2-	-	4.88 Å²	0 Å²
3-	-	-	-7.32 Å²

Refinement step

Cycle: LAST / Resolution: 3.24→49.75 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	11902	0	46	0	11948

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.008	0.022	12306
X-RAY DIFFRACTION	r_bond_other_d
X-RAY DIFFRACTION	r_angle_refined_deg	1.163	1.934	16754
X-RAY DIFFRACTION	r_angle_other_deg
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.905	5	1452
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	34.885	24.007	614
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	17.622	15	1986
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	16.843	15	58
X-RAY DIFFRACTION	r_chiral_restr	0.078	0.2	1758
X-RAY DIFFRACTION	r_gen_planes_refined	0.003	0.02	9530
X-RAY DIFFRACTION	r_gen_planes_other
X-RAY DIFFRACTION	r_nbd_refined	0.205	0.2	5479
X-RAY DIFFRACTION	r_nbd_other
X-RAY DIFFRACTION	r_nbtor_refined	0.314	0.2	8247
X-RAY DIFFRACTION	r_nbtor_other
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.136	0.2	434
X-RAY DIFFRACTION	r_xyhbond_nbd_other
X-RAY DIFFRACTION	r_metal_ion_refined
X-RAY DIFFRACTION	r_metal_ion_other
X-RAY DIFFRACTION	r_symmetry_vdw_refined	0.396	0.2	31
X-RAY DIFFRACTION	r_symmetry_vdw_other
X-RAY DIFFRACTION	r_symmetry_hbond_refined	0.242	0.2	3
X-RAY DIFFRACTION	r_symmetry_hbond_other
X-RAY DIFFRACTION	r_symmetry_metal_ion_refined
X-RAY DIFFRACTION	r_symmetry_metal_ion_other
X-RAY DIFFRACTION	r_mcbond_it	0.205	1.5	7386
X-RAY DIFFRACTION	r_mcbond_other
X-RAY DIFFRACTION	r_mcangle_it	0.366	2	11748
X-RAY DIFFRACTION	r_mcangle_other
X-RAY DIFFRACTION	r_scbond_it	0.578	3	5798
X-RAY DIFFRACTION	r_scbond_other
X-RAY DIFFRACTION	r_scangle_it	0.955	4.5	5006
X-RAY DIFFRACTION	r_scangle_other
X-RAY DIFFRACTION	r_long_range_B_refined
X-RAY DIFFRACTION	r_long_range_B_other
X-RAY DIFFRACTION	r_rigid_bond_restr
X-RAY DIFFRACTION	r_sphericity_free
X-RAY DIFFRACTION	r_sphericity_bonded

Refine LS restraints NCS

Dom-ID: 1 / Auth asym-ID: A / Ens-ID: 1 / Number: 5974 / Refine-ID: X-RAY DIFFRACTION

Type	Rms dev position (Å)	Weight position
tight positional	0.03	0.05
tight thermal	0.07	0.5

LS refinement shell

Resolution: 3.236→3.319 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.345	86	-
R_work	0.326	2354	-
obs	-	-	100 %

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	4.541	1.2092	-3.0897	3.6453	-1.8758	2.9468	-0.351	0.0959	-1.6257	-0.3701	-0.3594	0.1235	1.0546	-0.2088	0.7104	0.1738	0.0994	-0.0444	0.5216	0.0553	0.7124	-5.3384	14.2155	30.095
2	3.9331	0.4237	-0.0813	3.1843	-0.4517	3.618	-0.1919	0.3073	-1.1465	-0.4229	-0.0818	0.3073	1.0518	-0.2805	0.2737	-0.2285	-0.1639	0.1358	0.0084	-0.1918	-0.0203	-28.5127	21.2204	23.5853
3	2.0644	1.5182	-2.164	2.843	-2.057	3.1259	-0.2793	-0.0294	-0.0843	0.0436	0.2058	0.4821	0.6654	-0.444	0.0734	-0.5093	-0.0195	0.0143	-0.0761	-0.0461	-0.3593	-30.1322	36.4325	25.5941
4	2.4951	-0.6065	0.3838	3.3194	-0.7698	0.4441	0.2085	-0.8981	0.0711	1.1945	-0.3134	0.8775	-0.2201	-0.0435	0.1049	-0.0427	-0.1193	0.3374	0.3307	-0.0733	-0.4164	-31.3918	38.9268	45.636
5	6.3173	0.9172	0.3057	2.455	-1.9718	2.319	-0.1123	-1.0285	-0.6501	1.189	-0.139	0.2173	-0.0607	0.2428	0.2513	0.2225	-0.0327	-0.0914	0.4949	0.1198	-0.5561	-15.4586	32.1417	54.0449
6	3.865	-0.4213	-0.8703	3.2396	-0.8054	2.2032	-0.0488	-0.6221	-0.8045	0.7118	-0.4804	-0.6893	0.3135	0.6945	0.5291	-0.187	0.0709	-0.2535	0.4437	0.3029	-0.204	3.165	28.6782	40.8542
7	4.601	0.3592	-0.6996	2.945	-0.9449	4.0397	0.1409	-0.584	0.1558	0.678	-0.4714	-0.7382	-0.3247	0.6042	0.3305	-0.4269	-0.0664	-0.2087	0.0245	0.0118	-0.451	-1.4401	50.6043	34.5202
8	2.7149	-1.2967	-3.166	4.6436	1.3232	5.169	0.3038	-1.0178	0.1122	0.1066	-0.5408	0.0119	-0.7493	0.6824	0.2371	-0.4719	-0.0692	-0.2091	-0.1377	-0.1071	-0.5048	-8.3619	56.5813	26.4625
9	2.5807	-0.6677	-1.7304	2.804	-0.8205	4.8711	0.3121	-0.538	0.0116	-0.1609	-0.5244	-0.8219	0.2275	0.8316	0.2123	-0.6969	0.0814	-0.1135	-0.1784	0.0104	-0.3867	0.0419	46.2766	16.4535
10	6.2421	-1.7145	4.827	1.3955	-0.6254	4.2632	-0.3595	-0.4202	1.794	-0.1394	-0.3607	-0.1402	-1.1367	-0.1716	0.7201	0.2962	0.015	0.0791	0.3951	0.0079	0.5222	-3.9534	84.5922	-9.0291
11	2.9749	-1.1797	-0.3491	6.2752	-0.5695	5.7828	0.1013	-0.1589	0.8494	-0.2626	0.3559	1.1545	-1.2241	-0.7128	-0.4572	-0.0743	0.2925	-0.1642	0.0427	0.1326	0.1634	-27.5423	77.0707	-5.09
12	1.6185	-0.6392	0.9225	4.2664	-3.5223	6.3683	-0.0409	0.3048	0.353	-1.0912	0.3994	0.928	-0.1533	-1.0335	-0.3585	-0.3809	0.063	-0.368	0.1292	0.139	-0.2033	-28.5903	61.8239	-7.2122
13	1.7463	-0.5685	-1.6305	1.0365	0.1908	1.6581	-0.3995	1.1216	0.1345	-1.3086	0.2824	0.5993	0.0528	-1.0304	0.1172	0.6465	-0.0628	-0.6418	0.5644	0.1236	-0.2974	-27.5749	59.2817	-27.2619
14	8.6484	-1.2202	3.6198	4.3791	-3.2933	3.3555	-0.049	1.1131	0.1785	-1.4556	0.1307	0.26	0.2442	-0.0569	-0.0817	0.8919	-0.0939	-0.1223	0.225	0.0718	-0.5683	-10.9666	66.4176	-33.8861
15	2.3982	-0.2541	0.6037	2.365	-0.7678	2.9707	-0.0691	0.5166	0.6179	-1.2172	-0.1961	-0.7653	-0.3712	0.7524	0.2653	0.2081	-0.1142	0.243	0.0662	0.1219	-0.2305	6.0059	70.3151	-18.7345
16	4.9988	0.4443	0.5681	1.9563	-0.098	3.2458	-0.2445	0.267	-0.2274	-1.1611	-0.1022	-0.6845	0.4474	0.4437	0.3467	-0.0272	0.0749	0.1842	-0.2382	-0.0639	-0.4707	1.2207	48.2966	-12.8706
17	9.3972	-1.05	2.4072	4.8651	0.7045	4.7716	-0.0147	0.7419	-0.6649	-0.7937	-0.2254	-0.171	0.7761	0.3423	0.2402	-0.2445	0.0237	0.1756	-0.3241	-0.0009	-0.5484	-6.4129	42.1724	-5.6045
18	0.8101	1.0978	-1.0401	5.0768	-0.2739	3.364	0.2788	-0.388	-0.0385	-0.2498	-0.4266	-0.7308	0.1273	0.8514	0.1477	-0.6175	0.1106	-0.0086	-0.0843	0.0043	-0.4714	0.6032	52.6748	5.2342

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	40 - 90
2	X-RAY DIFFRACTION	2	A	91 - 206
3	X-RAY DIFFRACTION	3	A	207 - 284
4	X-RAY DIFFRACTION	4	A	285 - 358
5	X-RAY DIFFRACTION	5	A	359 - 429
6	X-RAY DIFFRACTION	6	A	430 - 578
7	X-RAY DIFFRACTION	7	A	579 - 671
8	X-RAY DIFFRACTION	8	A	672 - 712
9	X-RAY DIFFRACTION	9	A	713 - 766
10	X-RAY DIFFRACTION	10	B	40 - 90
11	X-RAY DIFFRACTION	11	B	91 - 206
12	X-RAY DIFFRACTION	12	B	207 - 284
13	X-RAY DIFFRACTION	13	B	285 - 358
14	X-RAY DIFFRACTION	14	B	359 - 429
15	X-RAY DIFFRACTION	15	B	430 - 578
16	X-RAY DIFFRACTION	16	B	579 - 671
17	X-RAY DIFFRACTION	17	B	672 - 712
18	X-RAY DIFFRACTION	18	B	713 - 766

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