PDB-7era: Crystal structure of human Biliverdin IX-beta reductase B with Ol...

ID or keywords:

Entry

Database: PDB / ID: 7era

Title

Crystal structure of human Biliverdin IX-beta reductase B with Olsalazine Sodium (OSS)

Components

Flavin reductase (NADPH)

Keywords

OXIDOREDUCTASE / platelets / Biliverdin reductase B / BLVRB / inhibitors / NADP / Olsalazine Sodium

Function / homology

Function and homology information

FMN reductase (NADH) 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 / megakaryocyte differentiation / riboflavin reductase (NADPH) activity / peptidyl-cysteine S-nitrosylase activity ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.35 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	7era.cif.gz	227.6 KB	Display	PDBx/mmCIF format
PDB format	pdb7era.ent.gz	150.1 KB	Display	PDB format
PDBx/mmJSON format	7era.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	7era_validation.pdf.gz	3.4 MB	Display	wwPDB validaton report
Full document	7era_full_validation.pdf.gz	3.4 MB	Display
Data in XML	7era_validation.xml.gz	25.3 KB	Display
Data in CIF	7era_validation.cif.gz	37 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/er/7era ftp://data.pdbj.org/pub/pdb/validation_reports/er/7era	HTTPS FTP

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Related structure data

Related structure data	7er6C 7er7C 7er8C 7er9C 7erbC 7ercC 7erdC 7ereC 1he5S S: Starting model for refinement C: citing same article (ref.)
Similar structure data	7er8-d 7ere-1 7erb-2 7erd-d 7erc-d 7erb-1 7er6-d 6rux-2 4k1s-d 6buv-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

47.2 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)	81.976, 117.225, 41.466
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-574- HOH
2	1	A-713- 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: 22286.494 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-JBC / 5-[(E)-(3-carboxy-4-oxidanyl-phenyl)diazenyl]-2-oxidanyl-benzoic acid Mass: 302.239 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₄H₁₀N₂O₆ / Feature type: SUBJECT OF INVESTIGATION / Comment: medication, antiinflammatory*YM
#4: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: SO₄ / Feature type: SUBJECT OF INVESTIGATION
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 524 / 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: 2.18 Å³/Da / Density % sol: 43.6 %
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: 0.97945 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: 0.97945 Å / Relative weight: 1
Reflection	Resolution: 1.35→47.68 Å / Num. obs: 88173 / % possible obs: 99.63 % / Redundancy: 10.6 % / B_iso Wilson estimate: 11.42 Å² / CC_1/2: 0.999 / R_merge(I) obs: 0.09388 / Net I/σ(I): 13.91
Reflection shell	Resolution: 1.35→1.399 Å / R_merge(I) obs: 0.4255 / Num. unique obs: 8590 / CC_1/2: 0.881

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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: 1.35→47.68 Å / SU ML: 0.1214 / Cross valid method: FREE R-VALUE / σ(F): 1.41 / Phase error: 16.7448
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.1738	1999	2.27 %
R_work	0.1543	86082	-
obs	0.1548	88081	99.63 %

Solvent computation

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

Displacement parameters

B_iso mean: 20.61 Å²

Refinement step

Cycle: LAST / Resolution: 1.35→47.68 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3116	0	170	524	3810

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0156	3432
X-RAY DIFFRACTION	f_angle_d	1.5683	4710
X-RAY DIFFRACTION	f_chiral_restr	0.1048	542
X-RAY DIFFRACTION	f_plane_restr	0.0102	594
X-RAY DIFFRACTION	f_dihedral_angle_d	13.2724	1902

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 (%)
1.35-1.38	0.2735	139	0.2412	5985	X-RAY DIFFRACTION	98.2
1.38-1.42	0.2375	142	0.223	6067	X-RAY DIFFRACTION	99.68
1.42-1.46	0.2024	140	0.2053	6070	X-RAY DIFFRACTION	99.86
1.46-1.51	0.2258	141	0.1775	6066	X-RAY DIFFRACTION	99.68
1.51-1.57	0.201	140	0.1632	6073	X-RAY DIFFRACTION	99.36
1.57-1.63	0.1925	142	0.1588	6089	X-RAY DIFFRACTION	99.68
1.63-1.7	0.2104	143	0.1578	6164	X-RAY DIFFRACTION	99.84
1.7-1.79	0.1709	142	0.152	6098	X-RAY DIFFRACTION	99.79
1.79-1.9	0.1845	143	0.1488	6135	X-RAY DIFFRACTION	99.65
1.9-2.05	0.18	141	0.1454	6140	X-RAY DIFFRACTION	99.65
2.05-2.26	0.1364	144	0.1407	6190	X-RAY DIFFRACTION	100
2.26-2.58	0.1686	145	0.1453	6209	X-RAY DIFFRACTION	99.84
2.58-3.26	0.1538	145	0.1491	6273	X-RAY DIFFRACTION	99.83

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	2.54379640555	-0.470270474381	0.0550038578395	5.34977022235	0.847796815016	4.20222356826	0.0996451524367	0.286166418611	0.16361443367	-0.324532031652	0.148556706606	-0.119526458996	0.0188507329503	0.230511697435	-0.217211044464	0.0476709755375	-0.00932665327485	-0.00532233709452	0.100870782424	0.0116955698811	0.0526271141724	-21.1828289729	6.48233371977	-14.7872766535
2	1.99723683284	0.165421620047	-0.332780664749	0.28655661193	-0.179306315007	1.24466947099	0.0772428590368	0.134455909808	0.486657709102	-0.0189199403951	0.0573387849146	0.064303505569	-0.228772994909	-0.102662212895	-0.133963884436	0.133708453524	0.015918362165	0.0239932292677	0.0908338326848	0.0355545963993	0.156764606391	-23.0118592435	13.9146532541	-10.3638736669
3	1.17777176058	0.120136145044	-0.891733876724	0.551246482356	-0.244261723382	2.54528842662	0.0389321153573	0.337419867614	0.147916145421	-0.0967648141504	0.0684947869754	0.0887709498095	-0.0354400638471	-0.262868943042	-0.0987276666962	0.084001920397	-2.95727587112E-5	-0.00820877366892	0.129128268601	0.0240096290391	0.065447873724	-30.9802003864	3.72653652881	-13.1480474092
4	2.04704237965	2.18332024856	-1.75332110603	3.30071237034	-2.89483642012	2.92366905517	0.142327431815	-0.220662931348	0.0975143704386	0.355541009726	-0.129171717266	0.156109022255	-0.277373484221	0.0773309281725	0.0674902802492	0.0920639016404	0.00231957776521	0.0120913180178	0.0897162288376	-0.0262176460437	0.0528365844645	-28.0799922107	4.50001493583	5.50104325523
5	2.99999734178	0.013755085037	0.129505190374	3.54852188764	2.94477016204	6.08920524271	-0.0485511791013	0.153422674477	-0.0879112371258	-0.0414328598691	0.00100730820825	0.108730680791	0.0607566688488	-0.156594479964	0.0749601211972	0.0616733082601	-0.0073252649037	-0.00738650524487	0.0681637281882	0.00673395759611	0.0509356832488	-30.4785950505	-4.68696573952	-8.87359143097
6	1.46053140911	0.474102067275	0.0452012414707	1.33384829189	0.551829285528	3.8015412733	0.0188537085873	-0.161782281092	-0.130805069628	0.121048656787	-0.00428890066759	-0.0831253029397	0.143187384547	0.0943762545224	-0.0199702540373	0.0713446019381	0.0135416613929	-0.00442813664225	0.0702468769961	0.00810288856172	0.0518759746271	-21.042429186	-5.80305218534	3.12716687849
7	2.46004370641	1.29968579161	0.0655551467562	2.05761109704	0.056630054891	0.674803944418	0.0234342427596	-0.176449580412	-0.0974096044708	0.0878342725803	-0.0241516974812	-0.215153380038	0.00718501182684	0.0858606125507	-0.0148261478951	0.0697263037619	0.00919672887178	-0.000327463448229	0.0753287212955	-0.0101857386056	0.071348138467	-10.6153168021	0.0527338369775	-0.682852775011
8	2.34431845859	1.55775663248	1.88433474683	3.68142651151	2.68376636672	7.87854096342	0.11891089904	0.113557261301	-0.0433310514231	-0.110513452964	0.0720732984134	-0.261673630399	0.0904459895264	0.129177843929	-0.17542210152	0.0485057813512	-0.00334710680106	0.0175389969705	0.0620324010832	-0.0118618710467	0.0753658178435	-11.1771557053	5.38365827204	-6.13545783938
9	1.56360564291	-0.153358816047	-0.959479080452	3.7110573059	-0.14914771807	2.01051330517	0.0468285826095	0.0651760052933	-0.17562966213	0.0372098085252	-0.0663150778051	-0.402238183666	0.125918796194	0.0628192618617	0.00809081254573	0.0415831803482	0.0272072898268	0.018561122295	0.111853826251	-0.0209865592798	0.140879909808	-7.37260694256	-1.20488263546	-3.61849122432
10	3.77993414456	0.0336371266457	0.444563435534	4.16807642025	0.982709200328	2.12106326665	0.0247776156521	-0.19054364461	-0.231099644088	0.169575793648	-0.0375528566937	0.077178568907	0.104797919167	0.0220652778955	0.0251321220656	0.105128674104	0.00710952595815	0.0029221567553	0.0669836290833	0.0392464607391	0.125717823926	-35.3284894922	-32.9145532091	4.22968510952
11	3.02629758033	-2.30850549043	1.00518643775	4.40155983641	-0.624008836944	2.97735434482	0.248975303976	0.445929914023	-0.076183068126	-0.641595334064	-0.28820098223	0.25912337926	-0.0179396124264	0.109956917401	0.0311922010271	0.169507023928	0.0139143577505	-0.0330728263928	0.120931415133	0.0212097585127	0.187315763403	-40.8622612672	-31.3065327403	-4.59186904339
12	1.12769327377	0.0181056841511	-0.142326210987	4.44345754373	0.506064242344	0.544559622167	0.0173736451795	-0.146672384632	-0.236796205559	0.101905870618	-0.0266793542979	0.248003574794	0.04201764712	-0.031410368227	0.000581395240405	0.0924139217028	0.0026418985072	0.0206975116449	0.129157487978	0.056583152977	0.146303029543	-44.5007524185	-22.0643567543	8.53468581834
13	1.61564942595	0.0655274057677	0.11410185827	3.70490164941	0.368686429257	0.0764835737003	-0.106367595985	-0.243204586961	-0.133492281156	0.195716245723	0.140434269936	0.215549393877	0.012068379398	-0.0184708525144	-0.0307477590766	0.119856308094	0.00646496995091	0.0133725924075	0.149926963064	0.0443992649823	0.089050853961	-41.7060114293	-17.1839649725	12.8892110502
14	2.57746432523	0.387398487706	-0.0917926619585	3.24343147368	1.03033995599	3.10264062733	-0.00526859269092	-0.508427987169	0.0568675369005	0.258435491167	0.121699514666	-0.277941687647	-0.0269584977728	0.508183901727	-0.125105600601	0.120287907066	0.00692104310116	-0.0282845419888	0.266636443939	-0.0119301865112	0.190291035628	-26.8334501538	-22.7920948516	13.3947239105
15	2.40385452856	0.278460662526	0.518678105118	6.00481281096	-0.0383200535655	2.35671622206	-0.17891991625	-0.0846545339198	-0.140387193984	0.306239911668	0.364942823547	-0.414018230108	0.18588523142	0.47449564961	-0.0150150133107	0.162844049197	0.0531710283317	-0.0530794494459	0.335464202801	0.0119127404332	0.134102501955	-28.2975362723	-24.3021486849	16.9273099999

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 48 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 49 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 141 )
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 142 through 174 )
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 175 through 190 )
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 191 through 206 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 0 through 26 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 27 through 57 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 58 through 122 )
13	X-RAY DIFFRACTION	13	chain 'B' and (resid 123 through 155 )
14	X-RAY DIFFRACTION	14	chain 'B' and (resid 156 through 190 )
15	X-RAY DIFFRACTION	15	chain 'B' and (resid 191 through 206 )

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