PDB-7er6: Crystal structure of human Biliverdin IX-beta reductase B

ID or keywords:

Entry

Database: PDB / ID: 7er6

Title

Crystal structure of human Biliverdin IX-beta reductase B

Components

Flavin reductase (NADPH)

Keywords

OXIDOREDUCTASE /

platelets /

Biliverdin reductase B /

BLVRB / inhibitors /

NADP / thrombocytopenia

Function / homology

Function and homology information

biliberdin reductase NAD+ activity / biliverdin reductase (NADPH) activity /

biliverdin reductase / biliverdin reductase (NAD(P)H) activity / flavin reductase (NADPH) / riboflavin reductase (NADPH) activity / heme catabolic process / Heme degradation /

terminal bouton / Cytoprotection by HMOX1 ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.6 Å

Authors

Griesinger, C. / Lee, D. / Ryu, K.S. / Kim, M. / Ha, J.H.

Citation

Journal: J.Med.Chem. / Year: 2022
Title: Repositioning Food and Drug Administration-Approved Drugs for Inhibiting Biliverdin IX beta Reductase B as a Novel Thrombocytopenia Therapeutic Target.
Authors: Kim, M. / Ha, J.H. / Choi, J. / Kim, B.R. / Gapsys, V. / Lee, K.O. / Jee, J.G. / Chakrabarti, K.S. / de Groot, B.L. / Griesinger, C. / Ryu, K.S. / Lee, D.

History

Deposition	May 6, 2021	Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0	Jan 19, 2022	Provider: repository / Type: Initial release
Revision 1.1	Feb 23, 2022	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID
Revision 1.2	Nov 29, 2023	Group: Data collection / Refinement description Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	7er6.cif.gz	218 KB	Display	PDBx/mmCIF format
PDB format	pdb7er6.ent.gz	143.5 KB	Display	PDB format
PDBx/mmJSON format	7er6.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/er/7er6 ftp://data.pdbj.org/pub/pdb/validation_reports/er/7er6	HTTPS FTP

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Related structure data

Related structure data	7er7C 7er8C 7er9C 7eraC 7erbC 7ercC 7erdC 7ereC 1he5S S: Starting model for refinement C: citing same article (ref.)
Similar structure data	7erb-2 7ere-1 7erc-d 7era-d 7er9-d 7erb-1 1vpa-d 3eey-4 7erd-d 7er8-d 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	#37 - Jan 2003 Serum Albumin similarity (1) #258 - Jun 2021 Glucocorticoid Receptor and Dexamethasone similarity (1)

Deposited unit

A: Flavin reductase (NADPH)

B: Flavin reductase (NADPH)

hetero molecules

46.1 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)	81.871, 117.440, 41.561
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	18
Space group name H-M	P2₁2₁2
Space group name Hall	P22ab
Symmetry operation	#1: x,y,z #2: x+1/2,-y+1/2,-z #3: -x+1/2,y+1/2,-z #4: -x,-y,z

Components on special symmetry positions

ID	Model	Components
1	1	A-573- HOH
2	1	A-644- HOH
3	1	A-684- HOH

#1: Protein	Flavin reductase (NADPH) / FR / Biliverdin reductase B / BVR-B / Biliverdin-IX beta-reductase / Green heme-binding protein / ...FR / Biliverdin reductase B / BVR-B / Biliverdin-IX beta-reductase / Green heme-binding protein / GHBP / NADPH-dependent diaphorase / NADPH-flavin reductase / FLR Mass: 22148.350 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BLVRB, FLR / Production host: Escherichia coli (E. coli) References: UniProt: P30043, flavin reductase (NADPH), biliverdin reductase
#2: Chemical	ChemComp-NAP / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE / Nicotinamide adenine dinucleotide phosphate Mass: 743.405 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₂₈N₇O₁₇P₃ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-SO4 / SULFATE ION / Sulfate Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO₄
#4: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 413 / 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: 2.26 Å³/Da / Density % sol: 45.46 %
Crystal grow	Temperature: 291.15 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: 1.9M-2.0M Ammonium sulfate, 0.1M Bis-tris (pH 6.5)

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: PAL/PLS / Beamline: 11C / Wavelength: 0.97942 Å
Detector	Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 10, 2020
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97942 Å / Relative weight: 1
Reflection	Resolution: 1.596→47.72 Å / Num. obs: 53419 / % possible obs: 98.58 % / Redundancy: 7.8 % / B_iso Wilson estimate: 15.47 Å² / CC_1/2: 0.971 / R_merge(I) obs: 0.09847 / Net I/σ(I): 13.85
Reflection shell	Resolution: 1.596→1.653 Å / R_merge(I) obs: 0.3736 / Num. unique obs: 5047 / CC_1/2: 0.666

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Processing

Software

Name	Version	Classification
HKL-2000	1.16_3549	data collection
HKL-2000	1.16_3549	data scaling
PHENIX		model building
PHENIX	1.19.2	refinement
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 1HE5

1he5

Resolution: 1.6→47.72 Å / SU ML: 0.1679 / Cross valid method: FREE R-VALUE / σ(F): 1.46 / Phase error: 17.4262
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.198	2000	3.74 %
R_work	0.1619	51422	-
obs	0.1632	53154	98.52 %

Solvent computation

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

Displacement parameters

B_iso mean: 23.9 Å²

Refinement step

Cycle: LAST / Resolution: 1.6→47.72 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3106	0	111	413	3630

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0097	3296
X-RAY DIFFRACTION	f_angle_d	1.1147	4516
X-RAY DIFFRACTION	f_chiral_restr	0.0639	532
X-RAY DIFFRACTION	f_plane_restr	0.0069	568
X-RAY DIFFRACTION	f_dihedral_angle_d	12.1279	2284

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 (%)
1.6-1.64	0.2705	133	0.2522	3398	X-RAY DIFFRACTION	92.73
1.64-1.68	0.2681	139	0.235	3595	X-RAY DIFFRACTION	97.65
1.68-1.73	0.2631	140	0.2283	3616	X-RAY DIFFRACTION	97.66
1.73-1.79	0.2727	140	0.2048	3567	X-RAY DIFFRACTION	98.22
1.79-1.85	0.2165	139	0.1862	3608	X-RAY DIFFRACTION	98.17
1.85-1.92	0.2267	142	0.1699	3635	X-RAY DIFFRACTION	98.23
1.92-2.01	0.2561	143	0.1686	3670	X-RAY DIFFRACTION	99.22
2.01-2.12	0.1769	143	0.158	3678	X-RAY DIFFRACTION	99.45
2.12-2.25	0.1936	143	0.1441	3689	X-RAY DIFFRACTION	99.51
2.25-2.42	0.1848	144	0.148	3703	X-RAY DIFFRACTION	99.41
2.42-2.67	0.2091	146	0.1607	3724	X-RAY DIFFRACTION	99.69
2.67-3.05	0.204	146	0.162	3766	X-RAY DIFFRACTION	99.69
3.05-3.85	0.161	147	0.1415	3792	X-RAY DIFFRACTION	99.62

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	1.19544218532	-0.21460536705	0.251235840527	2.6346543923	1.35913320271	2.64081526978	0.221877857397	0.249005069157	0.199200436713	-0.182024616975	0.130407721472	-0.203504987754	-0.289136764257	-0.0085844947895	-0.202035685401	0.112171646436	-0.00255329351372	0.0243619191327	0.141944138257	0.00926568886076	0.0994322308358	-21.2431163314	6.40668014308	-14.7474072171
2	1.31288395798	0.0567257888862	-0.134788925492	0.475722328094	-0.214867689603	0.960856110244	0.088663566777	0.113334222298	0.522849375316	-0.0603202665667	0.0646737969655	0.0547882211076	-0.187637619061	-0.117079078629	-0.101045601175	0.143384356024	0.0246114222387	0.0393525966879	0.105219473782	0.049751846402	0.172311870272	-25.1807240883	12.5889286453	-10.3685920701
3	0.841790244197	0.319829482717	-1.18762138017	0.498299814795	-0.305314265629	1.75273895209	0.0675486700621	0.476102363729	0.193451382911	-0.0791147851879	0.0168970696551	0.165976677234	-0.131977938393	-0.196065597314	-0.0785396448472	0.11899181827	0.0106000532087	-0.00175332211948	0.175531121532	0.0125931165398	0.0517498038681	-29.2323125406	1.77212719639	-14.8156692947
4	0.271635224685	0.220636070889	-0.578868916649	0.594296861288	-0.883324871459	1.69829829069	0.0724910607355	-0.155536104101	0.140238511408	0.173296935682	-0.0914179377506	0.0448522162663	-0.138429603127	0.031508005577	-0.000992334512411	0.144877784605	-0.000546192234342	0.0202268015305	0.135918080158	-0.0345467288505	0.10141340753	-27.9499928244	4.45120710462	5.49805577071
5	1.41871470204	0.17016430615	0.498058586569	1.78111140952	1.58787353041	4.40245583004	-0.0142099937255	0.0895112744029	-0.118264767375	0.0248117415053	-0.0618316571838	0.11330194377	0.142211775558	-0.171265825593	0.0520960688278	0.112251006643	-4.57352483787E-5	-0.00142610690505	0.123777506871	-0.00524391288895	0.0663496638969	-30.5720429995	-4.63007754544	-8.76735144393
6	1.33251593483	0.0978806968635	-0.485177485017	1.10527250364	0.323559111772	1.25212944407	-0.0739481451635	-0.148460383022	-0.153317699888	0.134275058032	0.0824796433584	-0.122561162426	0.0804090983878	0.251085381241	-0.0723906245648	0.122389994225	0.0268594012793	0.00532351953409	0.127968240937	-0.00369250021168	0.0818200939965	-17.7106866236	-5.25970910005	2.61974757067
7	0.716508901857	0.454064626082	-0.0171978912488	0.699451228784	0.914673088129	2.82205533652	0.0400166513872	-0.174079135048	-0.109277451235	0.019414524822	-0.0174427157347	-0.0613394090133	0.100993670856	-0.0661973184039	-0.00834468487243	0.1376330964	-0.000119064185137	0.00981584917568	0.135881091898	0.0129302406218	0.0706918401533	-24.4582904223	-6.50493789554	3.89026969365
8	1.91530109938	0.54070072406	0.13080735268	1.16229342022	-0.148401330297	0.229299795608	-0.0255051900257	-0.11428268615	-0.0849493781302	0.071429400296	0.0355911603245	-0.108349575507	0.0285825614733	0.0404910213873	0.000413034017828	0.0928113797933	-0.000822155313002	0.00646211375047	0.0909085285485	-0.013343158549	0.0664849386905	-16.2366887311	-2.42386235873	-2.73201391614
9	1.37557191523	-0.0535499216049	0.0345534851384	4.68056643755	-0.392181278042	1.08238652574	0.0191711714631	-0.296975862655	-0.00420504319117	0.396895652185	-0.0303774104431	-0.100725585517	-0.0467711316671	0.0931585059476	-0.0124872993956	0.116728720154	-0.00524988310253	-0.0272526909315	0.151991111958	-0.0390036181744	0.133641684215	-6.23541443283	2.10275439588	1.07373513801
10	0.943801824588	-0.185888063968	-0.127530165329	1.84376132479	-0.020420060684	0.601802774152	0.0423833050031	0.0386267447418	0.0144098181628	-0.0184315362414	0.0075943129937	-0.290965456363	-0.0155862980305	0.186078022131	-0.062252756253	0.100763956568	0.000297819617685	0.0057395361089	0.137562715275	-0.0425665486724	0.135433656888	-9.28573590991	1.74549385619	-4.9895876366
11	2.27347452781	0.0250467622576	0.210696516291	3.30070290089	0.147028126486	0.839765089487	0.00307837481372	-0.0697320168054	-0.145776218586	0.0813283486603	0.00300745408306	0.00457608639658	0.0571475989815	0.0997463189607	0.0380356094549	0.15267563264	0.0178717907355	-0.00328698093565	0.0953533919456	0.0590434799211	0.211323009015	-35.0740539005	-32.5689858383	3.43627718616
12	0.794998566445	-0.81067930411	0.606308984409	1.82286774706	-0.0871437820544	1.49619363635	0.0784799345561	0.165646860874	-0.0646370167601	-0.493216917896	-0.0970080659388	0.31131807755	-0.102831102186	0.0448220144122	0.0124396007688	0.235987861956	0.0224727955375	-0.056267989222	0.132130531265	0.0425527306137	0.309838867525	-40.832108732	-31.3732300888	-4.54986040806
13	0.599720827205	-0.573957795918	-0.370197838895	2.87430000549	0.268133752532	0.256949845999	-0.0165852005047	-0.225419246598	-0.312533870665	0.068014441396	-0.027337737433	0.3507777494	0.0298053761018	0.00929400954486	0.022315882247	0.148147240874	-0.00344544626044	0.0199112128429	0.162775504987	0.0883329347201	0.273876613558	-44.3962159197	-22.2053553764	8.55403440622
14	2.25119137522	1.69006624235	-1.29198178006	5.0662121223	-1.35697638048	1.29282846095	-0.134085734617	-0.342759443403	-0.129903435425	0.253577156912	0.0805823289003	0.181372000507	0.00364640485123	0.0267575130303	0.0253499724137	0.166040074162	0.0265675429498	0.0165883726507	0.223508212872	0.074706540525	0.175999179272	-44.4452136346	-14.2583339905	12.5019869744
15	2.2200378818	0.122657973971	-0.681788509584	1.66871825863	0.0688729489683	1.96356240762	0.0580287408733	-0.489751074483	-0.059793433433	0.26208415821	0.15155931858	-0.162133999045	-0.179788937807	0.379592557835	-0.0972403974253	0.193190526904	0.00482423254321	-0.00211026135782	0.269624260651	0.03767231531	0.189617471922	-29.3394086525	-21.5259098784	14.0812133769
16	0.306833425623	-0.0654519450821	-0.387177586942	2.67860619265	-0.0606303131564	2.46947448141	-0.0962724120406	-0.326458185448	-0.236962373135	0.245930221072	0.212108655637	-0.110327603199	0.187649166898	0.319353662732	-0.0401244408352	0.15261280593	0.0336465461666	-0.00921487732051	0.244031090905	0.0802431326652	0.215390183977	-28.6353477074	-26.1618308743	13.5349749784

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 1 through 13 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 14 through 57 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 58 through 73 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 74 through 85 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 86 through 101 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 102 through 122 )
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 123 through 142 )
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 143 through 155 )
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 156 through 174 )
10	X-RAY DIFFRACTION	10	chain 'A' and (resid 175 through 206 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 1 through 26 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 27 through 57 )
13	X-RAY DIFFRACTION	13	chain 'B' and (resid 58 through 122 )
14	X-RAY DIFFRACTION	14	chain 'B' and (resid 123 through 142 )
15	X-RAY DIFFRACTION	15	chain 'B' and (resid 143 through 174 )
16	X-RAY DIFFRACTION	16	chain 'B' and (resid 175 through 206 )

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Yorodumi