PDB-7erd: Crystal structure of human Biliverdin IX-beta reductase B with Fl...

ID or keywords:

Entry

Database: PDB / ID: 7erd

Title

Crystal structure of human Biliverdin IX-beta reductase B with Flunixin Meglumin (FMG)

Components

Flavin reductase (NADPH)

Keywords

OXIDOREDUCTASE / platelets / Biliverdin reductase B / BLVRB / inhibitors / NADP / Flunixin

Function / homology

Function and homology information

FMN reductase (NADH) activity / biliberdin reductase (NAD+) activity / biliverdin reductase (NADP+) activity / biliverdin reductase [NAD(P)+] activity / flavin reductase (NADPH) / FMN reductase (NAD(P)H) activity / FMN reductase (NADPH) activity / Oxidoreductases; Acting on the CH-CH group of donors; With NAD+ or NADP+ as acceptor / Transferases; Transferring nitrogenous groups; Transferring other nitrogenous groups / peptidyl-cysteine S-nitrosylase activity ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2 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	7erd.cif.gz	214.4 KB	Display	PDBx/mmCIF format
PDB format	pdb7erd.ent.gz	142.2 KB	Display	PDB format
PDBx/mmJSON format	7erd.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/7erd ftp://data.pdbj.org/pub/pdb/validation_reports/er/7erd	HTTPS FTP

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Related structure data

Related structure data	7er6C 7er7C 7er8C 7er9C 7eraC 7erbC 7ercC 7ereC 1he5S S: Starting model for refinement C: citing same article (ref.)
Similar structure data	7er8-d 7ere-2 7erb-2 4ng4-1 7era-d 3psq-d 4q2k-1 6b0y-d 2w35-1 3uwd-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

46.6 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)	81.821, 116.996, 41.615
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-507- HOH
2	1	B-562- 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 Mass: 743.405 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₂₈N₇O₁₇P₃ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-JBO / 2-[[2-methyl-3-(trifluoromethyl)phenyl]amino]pyridine-3-carboxylic acid Mass: 296.245 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₄H₁₁F₃N₂O₂ / Feature type: SUBJECT OF INVESTIGATION / Comment: antiinflammatory*YM
#4: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO₄ / Feature type: SUBJECT OF INVESTIGATION
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 207 / 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: 2.25 Å³/Da / Density % sol: 45.29 %
Crystal grow	Temperature: 291.15 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: 1.9-2.0M 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 PILATUS 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: 1.502→47.59 Å / Num. obs: 25824 / % possible obs: 99.49 % / Redundancy: 10 % / B_iso Wilson estimate: 26 Å² / CC_1/2: 0.999 / R_merge(I) obs: 0.09644 / Net I/σ(I): 14.58
Reflection shell	Resolution: 1.502→1.556 Å / R_merge(I) obs: 0.4497 / Num. unique obs: 6334 / CC_1/2: 0.737

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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: 2→47.59 Å / SU ML: 0.2361 / Cross valid method: FREE R-VALUE / σ(F): 1.46 / Phase error: 21.6248
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.229	2000	7.75 %
R_work	0.1796	23804	-
obs	0.1835	25804	92.53 %

Solvent computation

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

Displacement parameters

B_iso mean: 35.41 Å²

Refinement step

Cycle: LAST / Resolution: 2→47.59 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3106	0	148	207	3461

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0079	3333
X-RAY DIFFRACTION	f_angle_d	0.9657	4567
X-RAY DIFFRACTION	f_chiral_restr	0.0523	531
X-RAY DIFFRACTION	f_plane_restr	0.0067	572
X-RAY DIFFRACTION	f_dihedral_angle_d	11.9965	2289

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 (%)
2-2.05	0.3015	121	0.2669	1444	X-RAY DIFFRACTION	81.34
2.05-2.1	0.2936	131	0.2557	1550	X-RAY DIFFRACTION	85.29
2.1-2.16	0.3062	130	0.2556	1547	X-RAY DIFFRACTION	85.82
2.16-2.23	0.3002	131	0.2183	1564	X-RAY DIFFRACTION	86.75
2.23-2.31	0.2332	141	0.2093	1668	X-RAY DIFFRACTION	91.13
2.31-2.41	0.2637	141	0.2002	1678	X-RAY DIFFRACTION	93.38
2.41-2.52	0.2492	142	0.199	1708	X-RAY DIFFRACTION	94.24
2.52-2.65	0.2441	146	0.1954	1731	X-RAY DIFFRACTION	94.37
2.65-2.82	0.2921	143	0.1947	1707	X-RAY DIFFRACTION	92.96
2.82-3.03	0.2342	149	0.1893	1767	X-RAY DIFFRACTION	96.77
3.03-3.34	0.2348	152	0.1691	1806	X-RAY DIFFRACTION	98.19
3.34-3.82	0.2393	155	0.1542	1850	X-RAY DIFFRACTION	98.87
3.82-4.81	0.1562	153	0.1338	1827	X-RAY DIFFRACTION	96.82

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	1.48441572295	0.1470230567	0.278246052934	3.33292957143	0.635796904205	5.86478644713	0.32555398095	0.33337833567	0.170468919801	-0.311601096903	0.263203185191	-0.194933290612	-0.368851218181	-0.420300495788	-0.449181851334	0.213546942237	-0.0372842161851	0.0419992306976	0.175928720279	0.0321173481244	0.228317615475	-21.0300063724	6.30574617928	-14.6140101715
2	2.09874851283	-0.935006945457	-0.48098143806	1.80589356318	1.26891562918	2.65578371202	0.166164365861	0.00836553444217	0.482848457241	-0.223458809069	0.216545831767	-0.238098266653	-0.518568120662	-0.00296239927482	-0.451822491069	0.268517235294	-0.00626847145192	0.0642069940441	0.198172652262	0.0288859640949	0.219299343722	-19.2739540393	11.2532510195	-11.4399522631
3	2.14825901169	0.656111036529	-0.857079772001	1.2487843959	-0.447663916794	1.82209258516	0.0927192505802	0.118978524871	0.471541080726	-0.012293151986	-0.00219358323931	0.099008354056	-0.446391835526	-0.327112595784	-0.0685961449628	0.271125305436	0.0561443697124	0.00409468290547	0.212488868479	0.0115866426508	0.245536351988	-29.2347935612	7.98371112104	-7.24799994239
4	1.88988607081	0.195309847159	-0.0969935022713	2.0603005141	0.690977987154	4.33135071648	0.0125592742946	0.218210168277	-0.194143297132	-0.00831414508998	0.0576961527261	0.226238350321	0.0656457620872	-0.708499831099	-0.040435279295	0.18809481389	-0.0133792960495	-0.0112434747451	0.256551819917	-0.0067689148625	0.192745577474	-30.5135993426	-4.53331868742	-8.86668983793
5	1.85894680751	0.386419340186	-0.107762641845	2.04584210443	0.0767891063914	1.85681205649	0.00116699179293	-0.15733648764	-0.124237036901	0.0600055614932	0.13534744335	-0.352732569896	-0.10985401009	0.114867176713	-0.170543254338	0.164005972169	0.00816101280724	-0.0136135981978	0.125772646921	-0.0104253581715	0.196926739638	-17.5612955872	-5.34044287882	2.41549597785
6	1.13605996843	0.427333569256	0.115068227055	1.31323944314	0.287009015425	3.55240746851	0.0594208180287	-0.274431000312	-0.160649960513	0.13740484668	-0.106803255993	0.0656605182129	-0.141376863567	-0.341988982723	0.0601684987863	0.181788228615	-0.00952714109658	-0.00307128030181	0.186700889197	0.0109826477328	0.139123546651	-24.4783930873	-6.53654300689	3.83035591909
7	2.18193727067	0.426652259491	-0.161438419278	2.72348471482	0.690998916716	0.96049182305	0.028686360982	-0.22103618363	0.134799938797	0.287918127722	0.108582599365	-0.299991756015	-0.0170894372934	0.241690505687	-0.157360012299	0.211021483883	0.0226640765749	-0.021862329138	0.234987886406	-0.0554764730704	0.210343299069	-10.2415147799	0.209041738447	-0.362302041896
8	1.27060108105	0.127391637761	0.522017020754	2.27284390488	1.04524078208	3.14180906872	0.257038687175	0.00546939613105	0.0698072065572	-0.230038401895	0.18892075241	-0.431221964551	-0.243957966388	0.402130099208	-0.40384858916	0.187260075878	-0.0388160454673	0.0352655820636	0.254731365076	-0.0526823616078	0.203833332249	-11.1620437983	5.47027511139	-5.34518643988
9	1.8014224506	-0.230844960649	-0.160143218198	3.00400116194	-0.288500877745	1.19380472682	0.0107334401924	-0.0953449252874	-0.22039998007	-0.234501000059	0.231665546584	-0.908479622803	-0.0818463095751	0.324490099117	-0.245080253075	0.200590656239	-0.00304929565559	0.0375578841247	0.284865332652	-0.106868658022	0.332540665069	-7.50993356435	-1.26745088707	-4.02571856862
10	2.58377086009	-0.232619480858	0.428412085496	2.85122067375	0.604115191575	0.798158411981	-0.0733569566498	-0.0135158566626	-0.383261731767	0.0416906330083	0.105732487031	-0.019024495322	0.118422887719	-0.0385648782258	0.0149646675578	0.231706788563	0.0302205975317	0.0293695027705	0.240136385175	0.0881174051199	0.39930218427	-36.2158630052	-33.3218021848	2.55998708918
11	0.16853981088	-0.00790971726155	0.301765416381	1.62444171243	-0.703226164069	0.811434699627	0.245171106137	0.391505279104	-0.128960688648	-0.747861975604	-0.100848617081	0.200977716782	0.0262350567614	0.517804474954	0.0245825129707	0.552900929936	0.0598850125889	-0.0693395211071	0.535325360998	-0.0118848814633	0.496803411829	-37.0448045528	-30.1343920982	-8.99616548453
12	1.05028215715	-1.21380484485	-0.215743833967	2.40571239657	1.4189840511	1.05042133943	0.0351440516166	-0.0024100223924	-0.540830066937	-0.420334155549	-0.0833440342908	0.986607361068	0.041168775184	-0.0460932537777	0.105300465297	0.303742727554	0.0140077254686	-0.0288535784614	0.316757084256	0.10157382714	0.629874954645	-46.3735462734	-25.3589287386	1.70967449198
13	1.64342980888	-0.761418725981	-0.709413038741	3.1464579405	0.57562207009	1.94775812566	-0.197513565612	-0.577077799374	-0.527290581672	0.312998407821	0.0787285465401	0.387241376224	0.0475895236996	0.128432713195	0.104630659276	0.268345294389	0.0584515941756	0.0486344341242	0.386036408802	0.132636192136	0.354119088631	-43.9662362498	-18.3646826138	12.1736845798
14	2.00459546156	0.452256800248	-0.392322905979	2.83874064772	-0.17486858852	1.66508246356	-0.16052578621	-0.51090712079	-0.37468839914	0.332910903298	0.0872539127076	-0.170143111741	0.0160037113896	0.510006029697	0.0963429336309	0.269075605718	0.0622047102311	-0.00794983747786	0.381568719273	0.104870172033	0.31855388244	-29.291542585	-23.687801207	12.3342392894
15	2.29963134691	1.49304118819	-0.683854992518	8.13506268755	0.141546495713	4.47715019542	-0.00514893976819	-0.631215949662	-0.582248831851	0.842625913682	-0.032053778022	-0.80378197243	-0.143587280787	0.347967737512	-0.0976776125479	0.38409278948	0.125915879483	-0.11784843656	0.531623480263	0.134920055693	0.350745853486	-28.3851172362	-24.5224302072	16.7250627347

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 34 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 35 through 85 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 86 through 101 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 102 through 122 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 123 through 142 )
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 143 through 174 )
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 175 through 189 )
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 190 through 206 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 1 through 34 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 35 through 48 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 49 through 85 )
13	X-RAY DIFFRACTION	13	chain 'B' and (resid 86 through 142 )
14	X-RAY DIFFRACTION	14	chain 'B' and (resid 143 through 190 )
15	X-RAY DIFFRACTION	15	chain 'B' and (resid 191 through 206 )

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