PDB-8bo6: COAGULATION FACTOR XI PROTEASE DOMAIN IN COMPLEX WITH ACTIVE SITE...

ID or keywords:

Entry

Database: PDB / ID: 8bo6

Title

COAGULATION FACTOR XI PROTEASE DOMAIN IN COMPLEX WITH ACTIVE SITE INHIBITOR 2

Components

Coagulation factor XIa light chain

Keywords

BLOOD CLOTTING / S1 PROTEASE / SERINE PROTEASE / STRUCTURE-BASED DRUG DESIGN / ACTIVE SITE DIRECTED INHIBITOR / HYDROLASE

Function / homology

Function and homology information

coagulation factor XIa / serine-type aminopeptidase activity / Defective F9 activation / positive regulation of fibrinolysis / plasminogen activation / Intrinsic Pathway of Fibrin Clot Formation / blood coagulation / heparin binding / serine-type endopeptidase activity / extracellular space ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.25 Å

Authors

Schaefer, M. / Roehrig, S. / Ackerstaff, J. / Nunez, E.J. / Gericke, K.M. / Meier, K. / Tersteegen, A. / Stampfuss, J. / Ellerbrock, P. / Meibom, D. ...

Funding support

1items

Citation

Journal: J.Med.Chem. / Year: 2023
Title: Design and Preclinical Characterization Program toward Asundexian (BAY 2433334), an Oral Factor XIa Inhibitor for the Prevention and Treatment of Thromboembolic Disorders.
Authors: Roehrig, S. / Ackerstaff, J. / Jimenez Nunez, E. / Teller, H. / Ellerbrock, P. / Meier, K. / Heitmeier, S. / Tersteegen, A. / Stampfuss, J. / Lang, D. / Schlemmer, K.H. / Schaefer, M. / ...

History

Deposition	Nov 14, 2022	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Sep 13, 2023	Provider: repository / Type: Initial release
Revision 1.1	Sep 20, 2023	Group: Database references / Structure summary / Category: citation / entity / entity_name_com Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _entity.pdbx_description / _entity.pdbx_ec

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	8bo6.cif.gz	124.8 KB	Display	PDBx/mmCIF format
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Validation report

Summary document	8bo6_validation.pdf.gz	735.6 KB	Display	wwPDB validaton report
Full document	8bo6_full_validation.pdf.gz	737.4 KB	Display
Data in XML	8bo6_validation.xml.gz	14.5 KB	Display
Data in CIF	8bo6_validation.cif.gz	21.2 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/bo/8bo6 ftp://data.pdbj.org/pub/pdb/validation_reports/bo/8bo6	HTTPS FTP

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Related structure data

Related structure data	8bo3C 8bo4C 8bo5C 8bo7C 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	#25 - Jan 2002 Thrombin similarity (1) #75 - Mar 2006 Tissue Factor similarity (1) #83 - Nov 2006 Fibrin similarity (1)

Deposited unit

AAA: Coagulation factor XIa light chain

hetero molecules

27.9 kDa, 1 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)	59.120, 59.634, 67.053
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	Coagulation factor XIa light chain Mass: 26856.496 Da / Num. of mol.: 1 / Mutation: C500S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: F11 / Production host: Komagataella pastoris (fungus) / References: UniProt: P03951
#2: Chemical	ChemComp-QW0 / (~{E})-~{N}-[[5-(3-azanyl-1~{H}-indazol-6-yl)-4-chloranyl-1~{H}-imidazol-2-yl]methyl]-3-[5-chloranyl-2-(1,2,3,4-tetrazol-1-yl)phenyl]prop-2-enamide Mass: 495.324 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₁H₁₆Cl₂N₁₀O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-CIT / CITRIC ACID Mass: 192.124 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₆H₈O₇
#4: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₃H₈O₃
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 227 / Source method: isolated from a natural source / Formula: H₂O
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: 2.2 Å³/Da / Density % sol: 44.11 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 0.1M citrate buffer pH 4.5 and 20-30% PEG4000

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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 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 1, 2009
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1 Å / Relative weight: 1
Reflection	Resolution: 1.25→44.561 Å / Num. obs: 65835 / % possible obs: 99.4 % / Redundancy: 7.9 % / CC_1/2: 1 / R_rim(I) all: 0.049 / Net I/σ(I): 23.09
Reflection shell	Resolution: 1.25→1.28 Å / Mean I/σ(I) obs: 2.75 / Num. unique obs: 4814 / CC_1/2: 0.824 / R_rim(I) all: 0.825

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0267	refinement
XDS		data reduction
XSCALE		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: in house model

Resolution: 1.25→44.561 Å / Cor.coef. F_o:F_c: 0.985 / Cor.coef. F_o:F_c free: 0.973 / SU B: 1.472 / SU ML: 0.027 / Cross valid method: THROUGHOUT / ESU R: 0.033 / ESU R Free: 0.033
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.1407	888	1.349 %
R_work	0.1161	64947	-
all	0.116	-	-
obs	-	65835	99.413 %

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL PLUS MASK

Displacement parameters

B_iso mean: 20.377 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	1.257 Å²	0 Å²	-0 Å²
2-	-	-1.511 Å²	0 Å²
3-	-	-	0.254 Å²

Refinement step

Cycle: LAST / Resolution: 1.25→44.561 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1880	0	71	227	2178

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.013	0.013	2128
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.015	1964
X-RAY DIFFRACTION	r_angle_refined_deg	1.661	1.669	2905
X-RAY DIFFRACTION	r_angle_other_deg	1.483	1.595	4529
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.835	5	265
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	29.063	21.532	111
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	11.419	15	358
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	18.861	15	16
X-RAY DIFFRACTION	r_chiral_restr	0.089	0.2	269
X-RAY DIFFRACTION	r_chiral_restr_other	0.039	0.2	1
X-RAY DIFFRACTION	r_gen_planes_refined	0.011	0.02	2440
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	513
X-RAY DIFFRACTION	r_nbd_refined	0.197	0.2	378
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.191	0.2	1830
X-RAY DIFFRACTION	r_nbtor_refined	0.172	0.2	969
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.083	0.2	931
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.142	0.2	151
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.285	0.2	20
X-RAY DIFFRACTION	r_nbd_other	0.213	0.2	51
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.132	0.2	24
X-RAY DIFFRACTION	r_mcbond_it	1.886	1.729	1005
X-RAY DIFFRACTION	r_mcbond_other	1.874	1.723	1004
X-RAY DIFFRACTION	r_mcangle_it	2.4	2.607	1271
X-RAY DIFFRACTION	r_mcangle_other	2.405	2.613	1272
X-RAY DIFFRACTION	r_scbond_it	3.359	2.219	1123
X-RAY DIFFRACTION	r_scbond_other	3.358	2.221	1124
X-RAY DIFFRACTION	r_scangle_it	4.063	3.143	1627
X-RAY DIFFRACTION	r_scangle_other	4.062	3.145	1628
X-RAY DIFFRACTION	r_lrange_it	4.523	22.029	2418
X-RAY DIFFRACTION	r_lrange_other	4.353	21.397	2374
X-RAY DIFFRACTION	r_rigid_bond_restr	2.551	3	4092

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
1.25-1.282	0.253	65	0.22	4747	0.22	4840	0.819	0.832	99.4215	0.184
1.282-1.318	0.251	63	0.197	4629	0.198	4717	0.83	0.883	99.47	0.162
1.318-1.356	0.186	62	0.166	4507	0.166	4585	0.918	0.926	99.651	0.131
1.356-1.397	0.174	60	0.153	4386	0.153	4462	0.917	0.94	99.6414	0.119
1.397-1.443	0.163	58	0.137	4235	0.138	4306	0.949	0.951	99.6981	0.107
1.443-1.494	0.152	56	0.127	4144	0.128	4211	0.95	0.961	99.7388	0.101
1.494-1.55	0.147	54	0.114	3964	0.114	4025	0.966	0.969	99.8261	0.09
1.55-1.613	0.164	53	0.105	3841	0.106	3906	0.97	0.974	99.6928	0.084
1.613-1.685	0.143	50	0.1	3697	0.1	3754	0.975	0.978	99.8135	0.082
1.685-1.767	0.124	48	0.09	3518	0.09	3572	0.977	0.983	99.832	0.075
1.767-1.863	0.113	47	0.091	3379	0.091	3431	0.983	0.983	99.8543	0.079
1.863-1.975	0.12	43	0.092	3171	0.092	3221	0.977	0.984	99.7827	0.083
1.975-2.111	0.115	41	0.09	2998	0.09	3044	0.982	0.985	99.8357	0.086
2.111-2.28	0.111	38	0.093	2823	0.093	2862	0.984	0.985	99.9651	0.092
2.28-2.497	0.13	36	0.098	2599	0.098	2636	0.977	0.985	99.9621	0.1
2.497-2.791	0.123	32	0.102	2359	0.102	2391	0.983	0.985	100	0.11
2.791-3.22	0.127	29	0.111	2094	0.111	2128	0.982	0.984	99.765	0.124
3.22-3.939	0.136	24	0.114	1786	0.115	1829	0.981	0.986	98.9612	0.135
3.939-5.549	0.131	18	0.128	1332	0.128	1442	0.98	0.981	93.62	0.167
5.549-44.561	0.251	11	0.221	738	0.221	862	0.899	0.941	86.891	0.273

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