PDB-8k4z: Crystal structure of human MMP-7 in complex with inhibitor

ID or keywords:

Entry

Database: PDB / ID: 8k4z

Title

Crystal structure of human MMP-7 in complex with inhibitor

Components

Inhibitor
Matrilysin

Keywords

HYDROLASE / Matrilysin / Matrin / Matrix metalloproteinase-7 / Pump-1 protease / Uterine metalloproteinase

Function / homology

Function and homology information

matrilysin / antibacterial peptide secretion / antibacterial peptide biosynthetic process / membrane protein intracellular domain proteolysis / Assembly of collagen fibrils and other multimeric structures / Activation of Matrix Metalloproteinases / Collagen degradation / membrane protein ectodomain proteolysis / collagen catabolic process / extracellular matrix disassembly ...
Similarity search - Function

Biological species

Homo sapiens (human)
synthetic construct (others)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.7 Å

Authors

Kamitani, M. / Mima, M. / Oka, Y.

Funding support

1items

Citation

Journal: To Be Published
Title: Discovery of TP0628103: A Selective MMP-7 Inhibitor Based on the Mitigation of OATP Substrate Recognition through Isoelectric Point Shift Strategy
Authors: Oka, Y. / Abe-Sato, K. / Tabuse, H. / Yasukawa, Y. / Yahara, T. / Nishimoto, T. / Kamitani, M. / Fukunaga, T. / Ochiai, N. / Kumasaka-Abe, T. / Hitaka, K. / Gunji, E. / Ohara, H. / Takeda, T. ...

History

Deposition	Jul 20, 2023	Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0	Apr 17, 2024	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8k4z.cif.gz	55 KB	Display	PDBx/mmCIF format
PDB format	pdb8k4z.ent.gz	34.9 KB	Display	PDB format
PDBx/mmJSON format	8k4z.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8k4z_validation.pdf.gz	436.8 KB	Display	wwPDB validaton report
Full document	8k4z_full_validation.pdf.gz	437.6 KB	Display
Data in XML	8k4z_validation.xml.gz	9.4 KB	Display
Data in CIF	8k4z_validation.cif.gz	12.1 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/k4/8k4z ftp://data.pdbj.org/pub/pdb/validation_reports/k4/8k4z	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	#237 - Sep 2019 Nanodiscs and HDL similarity (15) #28 - Apr 2002 Anthrax Toxin similarity (1) #12 - Dec 2000 Pepsin similarity (1) #44 - Aug 2003 Calmodulin similarity (1) #56 - Aug 2004 Caspases similarity (1)

Deposited unit

A: Matrilysin

B: Inhibitor

hetero molecules

20.5 kDa, 2 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)	75.799, 75.799, 60.530
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	79
Space group name H-M	I4

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Protein / Protein/peptide , 2 types, 2 molecules AB

#1: Protein	Matrilysin / Matrin / Matrix metalloproteinase-7 / MMP-7 / Pump-1 protease / Uterine metalloproteinase Mass: 19344.727 Da / Num. of mol.: 1 / Mutation: E215Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MMP7, MPSL1, PUMP1 / Plasmid: pET28a(+) / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P09237, matrilysin
#2: Protein/peptide	Inhibitor Mass: 827.224 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

#1: Protein

Matrilysin / Matrin / Matrix metalloproteinase-7 / MMP-7 / Pump-1 protease / Uterine metalloproteinase

Mass: 19344.727 Da / Num. of mol.: 1 / Mutation: E215Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Gene: MMP7, MPSL1, PUMP1 / Plasmid: pET28a(+) / Production host:

Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P09237, matrilysin

#2: Protein/peptide

Inhibitor

Mass: 827.224 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

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Non-polymers , 5 types, 69 molecules

#3: Chemical	ChemComp-CA / CALCIUM ION Mass: 40.078 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Ca
#4: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#5: Chemical	ChemComp-IOD / IODIDE ION Mass: 126.904 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: I
#6: Chemical	ChemComp-CL / CHLORIDE ION Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#7: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 63 / Source method: isolated from a natural source / Formula: H₂O

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Details

Has ligand of interest	Y

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.16 Å³/Da / Density % sol: 42.93 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion / pH: 7.5 Details: 20% w/v Polyethylene glycol 3350, 100mM Bis-Tris propane pH7.5, 200mM Sodium iodide

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.00003 Å
Detector	Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 10, 2018
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.00003 Å / Relative weight: 1
Reflection	Resolution: 1.7→53.6 Å / Num. obs: 18920 / % possible obs: 99.9 % / Redundancy: 11.9 % / CC_1/2: 0.992 / Net I/σ(I): 7.9
Reflection shell	Resolution: 1.7→1.79 Å / Num. unique obs: 2753 / CC_1/2: 0.54

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0267	refinement
iMOSFLM		data reduction
SCALA		data scaling
MOLREP		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.7→53.598 Å / Cor.coef. F_o:F_c: 0.944 / Cor.coef. F_o:F_c free: 0.928 / SU B: 3.896 / SU ML: 0.116 / Cross valid method: THROUGHOUT / ESU R: 0.118 / ESU R Free: 0.116
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2392	913	4.827 %
R_work	0.203	18003	-
all	0.205	-	-
obs	-	18916	99.915 %

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: 18.838 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-1.469 Å²	0 Å²	0 Å²
2-	-	-1.469 Å²	0 Å²
3-	-	-	2.939 Å²

Refinement step

Cycle: LAST / Resolution: 1.7→53.598 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1340	0	6	63	1409

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.009	0.013	1382
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.017	1234
X-RAY DIFFRACTION	r_angle_refined_deg	1.555	1.702	1879
X-RAY DIFFRACTION	r_angle_other_deg	1.352	1.624	2842
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.892	5	162
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	30.937	21.642	67
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	13.236	15	201
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	23.558	15	7
X-RAY DIFFRACTION	r_chiral_restr	0.071	0.2	169
X-RAY DIFFRACTION	r_gen_planes_refined	0.008	0.02	1558
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	336
X-RAY DIFFRACTION	r_nbd_refined	0.207	0.2	296
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.185	0.2	1149
X-RAY DIFFRACTION	r_nbtor_refined	0.174	0.2	688
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.079	0.2	601
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.167	0.2	51
X-RAY DIFFRACTION	r_metal_ion_refined	0.124	0.2	16
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.111	0.2	18
X-RAY DIFFRACTION	r_nbd_other	0.157	0.2	60
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.155	0.2	7
X-RAY DIFFRACTION	r_mcbond_it	1.52	1.807	654
X-RAY DIFFRACTION	r_mcbond_other	1.52	1.803	653
X-RAY DIFFRACTION	r_mcangle_it	2.47	2.694	814
X-RAY DIFFRACTION	r_mcangle_other	2.468	2.7	815
X-RAY DIFFRACTION	r_scbond_it	1.886	2.058	727
X-RAY DIFFRACTION	r_scbond_other	1.888	2.058	724
X-RAY DIFFRACTION	r_scangle_it	3.14	2.989	1064
X-RAY DIFFRACTION	r_scangle_other	3.141	2.989	1062
X-RAY DIFFRACTION	r_lrange_it	5.948	33.82	6457
X-RAY DIFFRACTION	r_lrange_other	5.937	33.799	6429

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
1.7-1.744	0.32	83	0.312	1297	0.313	1380	0.679	0.685	100	0.285
1.744-1.792	0.285	57	0.302	1312	0.301	1369	0.548	0.544	100	0.269
1.792-1.844	0.337	77	0.3	1228	0.303	1309	0.495	0.524	99.6944	0.268
1.844-1.9	0.317	61	0.273	1228	0.274	1293	0.627	0.705	99.6906	0.234
1.9-1.963	0.237	45	0.246	1171	0.246	1216	0.785	0.772	100	0.212
1.963-2.031	0.281	60	0.219	1156	0.222	1216	0.842	0.849	100	0.186
2.031-2.108	0.261	50	0.201	1115	0.204	1165	0.849	0.892	100	0.175
2.108-2.194	0.233	42	0.195	1091	0.196	1133	0.921	0.904	100	0.165
2.194-2.291	0.196	75	0.19	984	0.191	1063	0.919	0.913	99.6237	0.158
2.291-2.403	0.264	52	0.183	962	0.187	1014	0.902	0.929	100	0.156
2.403-2.533	0.218	55	0.193	932	0.194	987	0.92	0.926	100	0.169
2.533-2.686	0.235	44	0.178	899	0.181	943	0.905	0.939	100	0.164
2.686-2.871	0.217	41	0.184	806	0.186	850	0.931	0.939	99.6471	0.166
2.871-3.1	0.205	34	0.172	789	0.173	823	0.943	0.952	100	0.162
3.1-3.395	0.209	18	0.183	720	0.184	738	0.94	0.948	100	0.173
3.395-3.794	0.235	34	0.164	647	0.168	681	0.942	0.957	100	0.157
3.794-4.377	0.197	37	0.166	569	0.168	607	0.958	0.959	99.8353	0.163
4.377-5.352	0.201	20	0.168	484	0.169	504	0.967	0.966	100	0.168
5.352-7.531	0.196	18	0.169	390	0.171	408	0.94	0.954	100	0.166
7.531-53.598	0.276	10	0.217	223	0.22	233	0.903	0.951	100	0.22

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