PDB-6wvh: Human VKOR with Brodifacoum

ID or keywords:

Entry

Database: PDB / ID: 6wvh

Title

Human VKOR with Brodifacoum

Components

Vitamin K epoxide reductase, termini restrained by green fluorescent protein

Keywords

OXIDOREDUCTASE / FLUORESCENT PROTEIN / Vitamin K epoxide Reductase (VKOR) / Vitamin K / warfarin / superwarfarin / Brodifacoum / vitamin K expoxide(KO) / membrane protein

Function / homology

Function and homology information

peptidyl-glutamic acid carboxylation / vitamin-K-epoxide reductase (warfarin-insensitive) activity / Metabolism of vitamin K / vitamin-K-epoxide reductase (warfarin-sensitive) / vitamin-K-epoxide reductase (warfarin-sensitive) activity / vitamin K metabolic process / positive regulation of coagulation / regulation of blood coagulation / quinone binding / : ...
Similarity search - Function

Biological species

Aequorea victoria (jellyfish)

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.99 Å

Authors

Liu, S. / Sukumar, N. / Li, W.

Funding support

United States, 6items

Organization	Grant number	Country
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)	R01 HL121718	United States
Other private	Forefront of Science Award	United States
Other private	MCII 2020-854	United States
National Institutes of Health/National Eye Institute (NIH/NEI)	R21 EY028705	United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	R01 GM131008	United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	P30 GM124165	United States

Citation

Journal: Science / Year: 2021
Title: Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation.
Authors: Liu, S. / Li, S. / Shen, G. / Sukumar, N. / Krezel, A.M. / Li, W.

History

Deposition	May 6, 2020	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Nov 11, 2020	Provider: repository / Type: Initial release
Revision 1.1	Nov 25, 2020	Group: Database references / Category: citation / citation_author Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2	Jan 13, 2021	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.year / _citation_author.identifier_ORCID
Revision 1.3	Oct 18, 2023	Group: Data collection / Database references / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ncs_dom_lim Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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
Revision 1.4	Nov 15, 2023	Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2

Structure viewer	Molecule: MolmilJmol/JSmol

-
Download

PDBx/mmCIF format	6wvh.cif.gz	396.3 KB	Display	PDBx/mmCIF format
PDB format	pdb6wvh.ent.gz	268.8 KB	Display	PDB format
PDBx/mmJSON format	6wvh.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Summary document	6wvh_validation.pdf.gz	1.2 MB	Display	wwPDB validaton report
Full document	6wvh_full_validation.pdf.gz	1.2 MB	Display
Data in XML	6wvh_validation.xml.gz	37.5 KB	Display
Data in CIF	6wvh_validation.cif.gz	52 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/wv/6wvh ftp://data.pdbj.org/pub/pdb/validation_reports/wv/6wvh	HTTPS FTP

-
Related structure data

Related structure data	6wv3C 6wv4C 6wv5C 6wv6C 6wv7C 6wv8C 6wv9C 6wvaC 6wvbC 6wviC 2b3pS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	6wv7-1 6wv5-d 4exn-2 6ghm-1 5hzo-d 6wv3-d 3qvl-d 5yel-1 3nxa-d 3qvk-d Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) 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	#174 - Jun 2014 GFP-like Proteins similarity (5) #42 - Jun 2003 Green Fluorescent Protein similarity (5) #217 - Jan 2018 Opioid Receptors similarity (1) #164 - Aug 2013 Serotonin Receptor similarity (1) #199 - Jul 2016 Monellin similarity (1) #208 - Apr 2017 Glucose Transporters similarity (1) #27 - Mar 2002 Bacteriorhodopsin similarity (1)

Deposited unit

A: Vitamin K epoxide reductase, termini restrained by green fluorescent protein

B: Vitamin K epoxide reductase, termini restrained by green fluorescent protein

hetero molecules

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

1

A: Vitamin K epoxide reductase, termini restrained by green fluorescent protein

hetero molecules

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

2

B: Vitamin K epoxide reductase, termini restrained by green fluorescent protein

hetero molecules

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

Unit cell

Length a, b, c (Å)	42.576, 82.593, 78.610
Angle α, β, γ (deg.)	93.417, 97.481, 104.685
Int Tables number	1
Space group name H-M	P1
Space group name Hall	P1
Symmetry operation	#1: x,y,z

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID
1	1
2	1

NCS domain segments:

Ens-ID: 1

Dom-ID	Component-ID	Beg auth comp-ID	Beg label comp-ID	End auth comp-ID	End label comp-ID	Selection details	Auth asym-ID	Label asym-ID	Auth seq-ID	Label seq-ID
1	1	SER	SER	LEU	LEU	(chain 'A' and (resid 2 through 297 or resid 299 through 384))	A	A	2 - 64	2 - 64
1	2	VAL	VAL	GLU	GLU	(chain 'A' and (resid 2 through 297 or resid 299 through 384))	A	A	68 - 297	66 - 295
1	3	SER	SER	HIS	HIS	(chain 'A' and (resid 2 through 297 or resid 299 through 384))	A	A	299 - 384	297 - 382
2	4	SER	SER	LEU	LEU	(chain 'B' and (resid 2 through 158 or (resid 159...	B	B	2 - 64	2 - 64
2	5	VAL	VAL	GLU	GLU	(chain 'B' and (resid 2 through 158 or (resid 159...	B	B	68 - 297	66 - 295
2	6	SER	SER	HIS	HIS	(chain 'B' and (resid 2 through 158 or (resid 159...	B	B	299 - 384	297 - 382

#1: Protein	Vitamin K epoxide reductase, termini restrained by green fluorescent protein / Vitamin K1 2 / 3-epoxide reductase subunit 1 Mass: 44197.434 Da / Num. of mol.: 2 Fragment: GPF (UNP residues 1-144) + VKOR + GFP (UNP residues 146-231) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Aequorea victoria (jellyfish), (gene. exp.) Homo sapiens (human) Gene: gfp, VKORC1, VKOR, MSTP134, MSTP576, UNQ308/PRO351 / Production host: Komagataella pastoris (fungus) References: UniProt: A0A059PIQ0, UniProt: Q9BQB6, UniProt: P42212*PLUS, vitamin-K-epoxide reductase (warfarin-sensitive)
#2: Chemical	ChemComp-UA7 / Brodifacoum / 3-[(1R,3S)-3-(4'-bromo[1,1'-biphenyl]-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl]-4-hydroxy-2H-1-benzopyran-2-one Mass: 523.417 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₃₁H₂₃BrO₃ / Feature type: SUBJECT OF INVESTIGATION / Comment: anticoagulant, antagonist*YM
#3: Chemical	ChemComp-OLC / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / 1-Oleoyl-R-glycerol Mass: 356.540 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C₂₁H₄₀O₄
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 461 / 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: 3.03 Å³/Da / Density % sol: 59.45 %
Crystal grow	Temperature: 295 K / Method: lipidic cubic phase / pH: 6.5 Details: 32% PEG400, 0.1 M ammonium acetate, 1% 1,2,3-heptanetriol, 0.1 M MES, pH 6.5

-
Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

APS

/ Beamline: 24-ID-C / Wavelength: 0.9791 Å

Detector

Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 11, 2017

Radiation

Monochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 0.9791 Å / Relative weight: 1

Reflection

Resolution: 1.99→50 Å / Num. obs: 63563 / % possible obs: 90.7 % / Redundancy: 2.3 % / B_iso Wilson estimate: 23.86 Å² / R_merge(I) obs: 0.068 / R_pim(I) all: 0.055 / R_rim(I) all: 0.088 / Χ²: 1.15 / Net I/σ(I): 9.2

Reflection shell

Diffraction-ID: 1

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique obs	CC_1/2	R_pim(I) all	R_rim(I) all	Χ²	% possible all
2-2.03	2.2	0.415	3260	0.747	0.343	0.541	0.995	91.7
2.03-2.07	2.3	0.372	3141	0.806	0.305	0.484	1.006	91.3
2.07-2.11	2.3	0.321	3215	0.829	0.264	0.417	1.072	91.3
2.11-2.15	2.3	0.283	3166	0.872	0.233	0.368	1.076	90.8
2.15-2.2	2.3	0.238	3203	0.913	0.196	0.31	1.107	91
2.2-2.25	2.3	0.227	3217	0.911	0.186	0.295	1.122	90.3
2.25-2.31	2.2	0.196	2959	0.927	0.162	0.256	1.178	86.4
2.31-2.37	2.3	0.164	3189	0.948	0.135	0.213	1.223	89.8
2.37-2.44	2.3	0.148	3214	0.957	0.121	0.193	1.209	92.8
2.44-2.52	2.3	0.123	3276	0.97	0.101	0.16	1.255	92.6
2.52-2.61	2.3	0.113	3188	0.972	0.092	0.146	1.181	92.1
2.61-2.71	2.3	0.099	3182	0.979	0.08	0.128	1.21	90.3
2.71-2.84	2.2	0.088	2984	0.981	0.072	0.115	1.268	85.1
2.84-2.99	2.3	0.079	3223	0.985	0.064	0.102	1.327	92.9
2.99-3.17	2.3	0.064	3281	0.989	0.051	0.083	1.306	93.7
3.17-3.42	2.3	0.054	3196	0.992	0.043	0.069	1.132	91.4
3.42-3.76	2.3	0.049	3020	0.993	0.039	0.063	1.092	85.9
3.76-4.31	2.3	0.04	3322	0.995	0.032	0.051	1.066	94.5
4.31-5.43	2.2	0.036	3119	0.996	0.028	0.046	1.002	89.2
5.43-50	2.3	0.034	3208	0.998	0.027	0.044	1.161	91.7

-
Processing

Software

Name	Version	Classification
PHENIX	1.17.1_3660	refinement
HKL-2000		data reduction
HKL-2000		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB entry 2B3P

2b3p

Resolution: 1.99→30.47 Å / SU ML: 0.182 / Cross valid method: FREE R-VALUE / σ(F): 1.97 / Phase error: 20.878
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.215	3223	5.07 %
R_work	0.1946	60321	-
obs	0.1956	63544	90.25 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Displacement parameters

B_iso mean: 29.69 Å²

Refinement step

Cycle: LAST / Resolution: 1.99→30.47 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	6123	0	98	461	6682

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0041	6375
X-RAY DIFFRACTION	f_angle_d	0.7935	8636
X-RAY DIFFRACTION	f_chiral_restr	0.0496	955
X-RAY DIFFRACTION	f_plane_restr	0.0049	1079
X-RAY DIFFRACTION	f_dihedral_angle_d	18.3477	2270

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 (%)
1.99-2.02	0.2752	123	0.2363	2424	X-RAY DIFFRACTION	80.91
2.02-2.05	0.2568	136	0.2354	2612	X-RAY DIFFRACTION	91.2
2.05-2.08	0.2717	146	0.2149	2613	X-RAY DIFFRACTION	91.15
2.08-2.12	0.235	150	0.2127	2688	X-RAY DIFFRACTION	90.87
2.12-2.16	0.2165	131	0.1996	2610	X-RAY DIFFRACTION	91.03
2.16-2.2	0.2174	130	0.196	2626	X-RAY DIFFRACTION	91.05
2.2-2.24	0.2484	131	0.1974	2700	X-RAY DIFFRACTION	89.79
2.24-2.29	0.2284	126	0.1941	2484	X-RAY DIFFRACTION	87
2.29-2.34	0.2113	127	0.1871	2571	X-RAY DIFFRACTION	87.91
2.35-2.4	0.2382	140	0.1896	2677	X-RAY DIFFRACTION	93.15
2.4-2.47	0.2021	162	0.1854	2708	X-RAY DIFFRACTION	92.76
2.47-2.54	0.2152	141	0.188	2672	X-RAY DIFFRACTION	92.47
2.54-2.62	0.2314	135	0.1888	2706	X-RAY DIFFRACTION	91.53
2.62-2.72	0.2167	142	0.1925	2578	X-RAY DIFFRACTION	89.92
2.72-2.83	0.2363	143	0.1953	2454	X-RAY DIFFRACTION	84.37
2.83-2.95	0.1985	156	0.1905	2667	X-RAY DIFFRACTION	92.89
2.95-3.11	0.1957	124	0.1867	2744	X-RAY DIFFRACTION	93.85
3.11-3.3	0.1955	182	0.1828	2677	X-RAY DIFFRACTION	92.32
3.3-3.56	0.1984	150	0.1825	2582	X-RAY DIFFRACTION	89.52
3.56-3.92	0.1994	131	0.186	2558	X-RAY DIFFRACTION	87.73
3.92-4.48	0.2012	140	0.1912	2714	X-RAY DIFFRACTION	94.16
4.48-5.64	0.242	142	0.1983	2563	X-RAY DIFFRACTION	87.97
5.64-30.47	0.197	135	0.2111	2693	X-RAY DIFFRACTION	92.6

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	1.35634405105	0.297989864784	-0.103155699003	2.36608707578	-0.815143874032	2.11954912562	-0.0398384889032	-0.0509375763068	0.0531765874479	0.0588618114275	-0.0456809088627	-0.0679022289903	-0.0009653669973	-0.00300030826214	0.0673636505388	0.0850311592993	0.0137541500088	-0.02597312848	0.0913815939318	-0.0293766840028	0.148855187991	33.4361897738	-59.5801623452	51.5315168055
2	2.88602280409	-1.0730526498	-0.0865895968451	2.18297297813	0.134648588245	1.45973590771	-0.101125889598	-0.155929969937	-0.115907474297	0.437065882116	0.142073174616	0.128152956379	0.197140047679	-0.0367556527839	-0.0203639831183	0.28497640807	0.0240833962666	-0.00736698163853	0.178869466625	-0.0342410902681	0.136385869097	27.3973269334	-13.5924745997	54.7034115916
3	1.36840713977	0.537683019315	-0.601214234268	2.28335291993	-0.606861603589	1.68385177559	-0.00906269748874	-0.0758770735861	0.0720315299573	0.161441589979	-0.0496822854013	0.136107269754	-0.138543644786	-0.118697339299	0.0387421175074	0.159641948093	0.0313361108815	-0.0292271642193	0.158361630166	-0.0404060132142	0.198240104106	28.0325393325	-54.8969583288	55.7588372692
4	1.60282917643	-0.624143276957	0.270786584924	1.81949682673	-0.353698182627	2.24395622429	-0.0407350252476	0.0533197262186	0.128605934039	-0.0680327239377	-0.0493425756362	-0.11817420353	-0.0566590537132	0.0495779206786	0.0656286896722	0.0860018741292	-0.0346392290715	0.016956067482	0.0985707887732	0.0021607790751	0.139445023919	33.66890767	15.1828714705	20.5542762168
5	2.39782669097	0.714633839317	0.287731846131	2.57631720071	0.527937452532	1.9247206704	-0.101599011611	0.155075961176	0.0303408848705	-0.48150687277	0.184076882521	0.0717576596798	-0.262327572425	-0.131989590799	-0.0658423275728	0.267221977492	-0.0208528583223	0.0263607601854	0.19298747414	-0.012281351026	0.139605230535	27.5305444596	-30.4023047908	17.5796405891
6	0.41887661763	-0.181838300259	0.112656936147	0.493863749118	-0.339633897127	1.37386807895	-0.0138316109407	0.00193104881101	0.0492577964325	-0.0650852069583	-0.049147529717	-0.0313049980671	0.0845299104146	-0.0786521701642	0.0829672825563	0.183168406581	-0.0168618975029	0.00842415980678	0.144253039211	-0.0149849805896	0.195355213867	28.0081573712	10.5587643557	13.6387823335

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 2 through 151 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 152 through 296 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 297 through 384 )
4	X-RAY DIFFRACTION	4	chain 'B' and (resid 2 through 151 )
5	X-RAY DIFFRACTION	5	chain 'B' and (resid 152 through 298 )
6	X-RAY DIFFRACTION	6	chain 'B' and (resid 299 through 392 )

-
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://pdbjlvh1.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