PDB-8aai: Crystal structure of the PDZ tandem of syntenin in complex with f...

ID or keywords:

Entry

Database: PDB / ID: 8aai

Title

Crystal structure of the PDZ tandem of syntenin in complex with fragment E5

Components

Syntenin-1

Keywords

SIGNALING PROTEIN / signaling protein cell adhesion PDZ domain syntenin syndecan drug design

Function / homology

Function and homology information

interleukin-5 receptor complex / interleukin-5 receptor binding / positive regulation of extracellular exosome assembly / syndecan binding / Neurofascin interactions / cytoskeletal anchor activity / substrate-dependent cell migration, cell extension / positive regulation of exosomal secretion / negative regulation of receptor internalization / frizzled binding ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.76 Å

Authors

Feracci, M. / Barral, K.

Funding support

France, 1items

Citation

Journal: J.Med.Chem. / Year: 2023
Title: Discovery of a PDZ Domain Inhibitor Targeting the Syndecan/Syntenin Protein-Protein Interaction: A Semi-Automated "Hit Identification-to-Optimization" Approach.
Authors: Hoffer, L. / Garcia, M. / Leblanc, R. / Feracci, M. / Betzi, S. / Ben Yaala, K. / Daulat, A.M. / Zimmermann, P. / Roche, P. / Barral, K. / Morelli, X.

History

Deposition	Jul 1, 2022	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Apr 26, 2023	Provider: repository / Type: Initial release
Revision 1.1	Feb 7, 2024	Group: Data collection / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_ncs_dom_lim Item: _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id ..._struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

Structure viewer	Molecule: MolmilJmol/JSmol

-
Download

PDBx/mmCIF format	8aai.cif.gz	261.3 KB	Display	PDBx/mmCIF format
PDB format	pdb8aai.ent.gz	206.5 KB	Display	PDB format
PDBx/mmJSON format	8aai.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Summary document	8aai_validation.pdf.gz	1.4 MB	Display	wwPDB validaton report
Full document	8aai_full_validation.pdf.gz	1.4 MB	Display
Data in XML	8aai_validation.xml.gz	31.1 KB	Display
Data in CIF	8aai_validation.cif.gz	39.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/aa/8aai ftp://data.pdbj.org/pub/pdb/validation_reports/aa/8aai	HTTPS FTP

-
Related structure data

Related structure data	8aakC 8aaoC 8aapC 1n99S S: Starting model for refinement C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

-
Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#245 - May 2020 Spliceosomes similarity (1) #141 - Sep 2011 O-GlcNAc Transferase similarity (1) #43 - Jul 2003 Src Tyrosine Kinase similarity (1) #60 - Dec 2004 Ubiquitin similarity (1) #56 - Aug 2004 Caspases similarity (1)

Deposited unit

A: Syntenin-1

B: Syntenin-1

C: Syntenin-1

D: Syntenin-1

hetero molecules

73.3 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Syntenin-1

C: Syntenin-1

hetero molecules

defined by author
Evidence: fluorescence resonance energy transfer, HTRF
36.6 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Syntenin-1

D: Syntenin-1

hetero molecules

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

Unit cell

Length a, b, c (Å)	29.114, 56.130, 102.867
Angle α, β, γ (deg.)	82.710, 83.462, 77.033
Int Tables number	1
Space group name H-M	P1

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	A
2	1	A
3	2	A
4	2	A
5	3	A
6	3	A
7	4	A
8	4	A
9	5	A
10	5	A
11	6	A
12	6	A

NCS domain segments:

Beg auth comp-ID: ASP / Beg label comp-ID: ASP / End auth comp-ID: ALA / End label comp-ID: ALA / Refine code: 1 / Auth asym-ID: A / Label asym-ID: A / Auth seq-ID: 111 - 272 / Label seq-ID: 4 - 165

Dom-ID	Component-ID	Ens-ID
1	1	1
2	1	1
3	2	2
4	2	2
5	3	3
6	3	3
7	4	4
8	4	4
9	5	5
10	5	5
11	6	6
12	6	6

NCS ensembles :

ID	Details
1	Local NCS retraints between domains: 1 2
2	Local NCS retraints between domains: 3 4
3	Local NCS retraints between domains: 5 6
4	Local NCS retraints between domains: 7 8
5	Local NCS retraints between domains: 9 10
6	Local NCS retraints between domains: 11 12

#1: Protein	Syntenin-1 / Melanoma differentiation-associated protein 9 / MDA-9 / Pro-TGF-alpha cytoplasmic domain- ...Melanoma differentiation-associated protein 9 / MDA-9 / Pro-TGF-alpha cytoplasmic domain-interacting protein 18 / TACIP18 / Scaffold protein Pbp1 / Syndecan-binding protein 1 Mass: 18018.688 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SDCBP, MDA9, SYCL / Production host: Escherichia coli (E. coli) / References: UniProt: O00560
#2: Chemical	ChemComp-LKV / (2~{S})-2-[[(2~{S})-3-methyl-2-(3-oxidanylidene-1~{H}-isoindol-2-yl)butanoyl]amino]propanoic acid Mass: 304.341 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₁₆H₂₀N₂O₄ / Feature type: SUBJECT OF INVESTIGATION
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 188 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

-
Experiment

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

-
Sample preparation

Crystal	Density Matthews: 2.25 Å³/Da / Density % sol: 45.23 %
Crystal grow	Temperature: 297 K / Method: vapor diffusion, sitting drop Details: 100mM Sodium Acetate 200mM Ammonium acetate 20% PEG 3350 PH range: 4.4 - 4.8

-
Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 0.97625 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 19, 2017
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97625 Å / Relative weight: 1
Reflection	Resolution: 2.76→27.63 Å / Num. obs: 15909 / % possible obs: 97.29 % / Redundancy: 5.27 % / R_merge(I) obs: 0.1388 / R_pim(I) all: 0.08908 / Net I/σ(I): 5.27
Reflection shell	Resolution: 2.76→2.859 Å / R_merge(I) obs: 0.4417 / Mean I/σ(I) obs: 2.26 / Num. unique obs: 1613 / R_pim(I) all: 0.288 / % possible all: 96.74

-
Processing

Software

Name	Version	Classification
REFMAC	5.8.0350	refinement
xia2	XIA2 0.5.337-g4c821dce-dials-1.6	data reduction
DIALS	DIALS 1.6.3-g2108d754-release	data scaling
PHASER	2.8.3	phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 1N99

1n99

Resolution: 2.76→27.63 Å / Cor.coef. F_o:F_c: 0.895 / Cor.coef. F_o:F_c free: 0.871 / SU B: 26.151 / SU ML: 0.507 / Cross valid method: FREE R-VALUE / ESU R Free: 0.528
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.3171	782	4.942 %
R_work	0.2746	15041	-
all	0.277	-	-
obs	-	15823	98.006 %

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: 50.548 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	7.622 Å²	-1.163 Å²	-0.676 Å²
2-	-	-2.241 Å²	2.756 Å²
3-	-	-	-5.081 Å²

Refinement step

Cycle: LAST / Resolution: 2.76→27.63 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	4928	0	88	188	5204

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.003	0.012	5092
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	4830
X-RAY DIFFRACTION	r_angle_refined_deg	0.737	1.62	6870
X-RAY DIFFRACTION	r_angle_other_deg	0.294	1.583	11271
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.24	5	646
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	10.986	10	28
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	13.276	10	937
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	11.576	10	209
X-RAY DIFFRACTION	r_chiral_restr	0.036	0.2	809
X-RAY DIFFRACTION	r_gen_planes_refined	0.003	0.02	5912
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	912
X-RAY DIFFRACTION	r_nbd_refined	0.18	0.2	1079
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.177	0.2	4711
X-RAY DIFFRACTION	r_nbtor_refined	0.155	0.2	2538
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.077	0.2	2852
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.13	0.2	166
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.103	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.171	0.2	27
X-RAY DIFFRACTION	r_nbd_other	0.159	0.2	90
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.104	0.2	5
X-RAY DIFFRACTION	r_mcbond_it	1.432	5.34	2593
X-RAY DIFFRACTION	r_mcbond_other	1.432	5.34	2593
X-RAY DIFFRACTION	r_mcangle_it	2.538	8.005	3240
X-RAY DIFFRACTION	r_mcangle_other	2.538	8.005	3240
X-RAY DIFFRACTION	r_scbond_it	1.142	5.499	2499
X-RAY DIFFRACTION	r_scbond_other	1.141	5.5	2498
X-RAY DIFFRACTION	r_scangle_it	2.07	8.174	3630
X-RAY DIFFRACTION	r_scangle_other	2.07	8.174	3630
X-RAY DIFFRACTION	r_lrange_it	5.777	76.721	5582
X-RAY DIFFRACTION	r_lrange_other	5.744	76.788	5564
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.114	0.05	4440
X-RAY DIFFRACTION	r_ncsr_local_group_2	0.12	0.05	4494
X-RAY DIFFRACTION	r_ncsr_local_group_3	0.117	0.05	4444
X-RAY DIFFRACTION	r_ncsr_local_group_4	0.131	0.05	4453
X-RAY DIFFRACTION	r_ncsr_local_group_5	0.123	0.05	4406
X-RAY DIFFRACTION	r_ncsr_local_group_6	0.11	0.05	4512

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Refine-ID	Type	Rms dev position (Å)	Weight position
1	1	A	X-RAY DIFFRACTION	Local ncs	0.11424	0.05009
1	2	A	X-RAY DIFFRACTION	Local ncs	0.11424	0.05009
2	3	A	X-RAY DIFFRACTION	Local ncs	0.11961	0.0501
2	4	A	X-RAY DIFFRACTION	Local ncs	0.11961	0.0501
3	5	A	X-RAY DIFFRACTION	Local ncs	0.11662	0.0501
3	6	A	X-RAY DIFFRACTION	Local ncs	0.11662	0.0501
4	7	A	X-RAY DIFFRACTION	Local ncs	0.13127	0.05009
4	8	A	X-RAY DIFFRACTION	Local ncs	0.13127	0.05009
5	9	A	X-RAY DIFFRACTION	Local ncs	0.12277	0.0501
5	10	A	X-RAY DIFFRACTION	Local ncs	0.12277	0.0501
6	11	A	X-RAY DIFFRACTION	Local ncs	0.11048	0.0501
6	12	A	X-RAY DIFFRACTION	Local ncs	0.11048	0.0501

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 (%)
2.76-2.832	0.346	72	0.37	1083	X-RAY DIFFRACTION	96.7337
2.832-2.909	0.299	64	0.34	1112	X-RAY DIFFRACTION	98.2456
2.909-2.993	0.287	49	0.295	1048	X-RAY DIFFRACTION	97.5979
2.993-3.085	0.319	48	0.282	995	X-RAY DIFFRACTION	98.2109
3.085-3.186	0.294	46	0.286	1035	X-RAY DIFFRACTION	98.2727
3.186-3.297	0.289	45	0.275	946	X-RAY DIFFRACTION	97.6355
3.297-3.421	0.389	44	0.243	910	X-RAY DIFFRACTION	98.7578
3.421-3.56	0.27	51	0.248	915	X-RAY DIFFRACTION	96.6
3.56-3.718	0.278	53	0.227	814	X-RAY DIFFRACTION	97.8555
3.718-3.898	0.284	35	0.225	811	X-RAY DIFFRACTION	98.4866
3.898-4.108	0.363	53	0.245	795	X-RAY DIFFRACTION	97.9215
4.108-4.356	0.306	25	0.224	725	X-RAY DIFFRACTION	97.9112
4.356-4.654	0.368	41	0.259	699	X-RAY DIFFRACTION	98.5353
4.654-5.024	0.296	45	0.229	633	X-RAY DIFFRACTION	99.2679
5.024-5.499	0.262	34	0.27	596	X-RAY DIFFRACTION	99.3691
5.499-6.14	0.301	16	0.291	553	X-RAY DIFFRACTION	98.4429
6.14-7.075	0.577	25	0.348	482	X-RAY DIFFRACTION	97.6879
7.075-8.629	0.259	15	0.273	392	X-RAY DIFFRACTION	98.5472
8.629-12.053	0.352	15	0.318	311	X-RAY DIFFRACTION	97.8979
12.053-27.63	0.536	6	0.457	186	X-RAY DIFFRACTION	96.9697

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

Version 3 of the EMDB header file is now the official format.
The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

Thousand views of thousand structures

Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

-Movie

-Structure viewers

+Viewer log

-This page

-This web site

-Options

+Open data

-Basic information

-Structure visualization

-Downloads & links

-Download

-Validation report

-Related structure data

-Links

-Assembly

-Components

-Experimental details

-Experiment

-Sample preparation

-Data collection

-Processing

+About Yorodumi

-News

-Feb 9, 2022. New format data for meta-information of EMDB entries

-Aug 12, 2020. Covid-19 info

+Mar 5, 2020. Novel coronavirus structure data

+Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+Jul 12, 2017. Major update of PDB

-Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi