PDB-7er8: Crystal structure of human Biliverdin IX-beta reductase B with Su...

ID or keywords:

Entry

Database: PDB / ID: 7er8

Title

Crystal structure of human Biliverdin IX-beta reductase B with Sulfasalazine (SAS)

Components

Flavin reductase (NADPH)

Keywords

OXIDOREDUCTASE / platelets / Biliverdin reductaseB / BLVRB / inhibitors / NADP / Sulfasalazine

Function / homology

Function and homology information

FMN reductase (NADH) activity / biliverdin reductase [NAD(P)H] activity / flavin reductase (NADPH) / 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 / heme catabolic process / Heme degradation ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.45 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	7er8.cif.gz	223.1 KB	Display	PDBx/mmCIF format
PDB format	pdb7er8.ent.gz	146.9 KB	Display	PDB format
PDBx/mmJSON format	7er8.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	7er8_validation.pdf.gz	2.9 MB	Display	wwPDB validaton report
Full document	7er8_full_validation.pdf.gz	2.9 MB	Display
Data in XML	7er8_validation.xml.gz	24.1 KB	Display
Data in CIF	7er8_validation.cif.gz	34.1 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/er/7er8 ftp://data.pdbj.org/pub/pdb/validation_reports/er/7er8	HTTPS FTP

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Related structure data

Related structure data	7er6C 7er7C 7er9C 7eraC 7erbC 7ercC 7erdC 7ereC 1he5S S: Starting model for refinement C: citing same article (ref.)
Similar structure data	7erd-d 7era-d 7ere-2 7erb-2 6rux-2 7ere-1 6rqg-2 7d53-1 2x0k-2 3psq-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

49.8 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)	82.160, 117.367, 41.606
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-552- HOH
2	1	A-664- 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: 23529.822 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-SAS / 2-HYDROXY-(5-([4-(2-PYRIDINYLAMINO)SULFONYL]PHENYL)AZO)BENZOIC ACID / SULFASALAZINE Mass: 398.393 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₈H₁₄N₄O₅S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: SO₄ / Feature type: SUBJECT OF INVESTIGATION
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 380 / 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: 43.98 %
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: 1.446→50 Å / Num. obs: 72377 / % possible obs: 99.39 % / Redundancy: 9.8 % / B_iso Wilson estimate: 14.04 Å² / CC_1/2: 0.999 / R_merge(I) obs: 0.09682 / Net I/σ(I): 15.11
Reflection shell	Resolution: 1.446→1.498 Å / R_merge(I) obs: 0.4523 / Num. unique obs: 6896 / CC_1/2: 0.721

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Processing

Software

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

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 1HE5

1he5

Resolution: 1.45→47.75 Å / SU ML: 0.1424 / Cross valid method: FREE R-VALUE / σ(F): 1.42 / Phase error: 18.1207
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.1991	2000	2.76 %
R_work	0.1655	70377	-
obs	0.1664	72377	99.31 %

Solvent computation

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

Displacement parameters

B_iso mean: 25.22 Å²

Refinement step

Cycle: LAST / Resolution: 1.45→47.75 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3116	0	177	380	3673

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0144	3395
X-RAY DIFFRACTION	f_angle_d	1.4696	4659
X-RAY DIFFRACTION	f_chiral_restr	0.1033	536
X-RAY DIFFRACTION	f_plane_restr	0.0089	584
X-RAY DIFFRACTION	f_dihedral_angle_d	9.5699	1895

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 (%)
1.45-1.48	0.2563	133	0.2446	4673	X-RAY DIFFRACTION	93.89
1.48-1.52	0.2208	141	0.2227	4977	X-RAY DIFFRACTION	99.46
1.52-1.57	0.2299	141	0.207	4940	X-RAY DIFFRACTION	99.39
1.57-1.62	0.2418	142	0.1943	5020	X-RAY DIFFRACTION	99.73
1.62-1.67	0.2178	142	0.183	4984	X-RAY DIFFRACTION	99.77
1.67-1.74	0.2295	142	0.179	4993	X-RAY DIFFRACTION	99.69
1.74-1.82	0.1891	142	0.1695	5013	X-RAY DIFFRACTION	99.56
1.82-1.92	0.1989	143	0.1643	5017	X-RAY DIFFRACTION	99.71
1.92-2.04	0.2031	143	0.1597	5012	X-RAY DIFFRACTION	99.9
2.04-2.19	0.1984	144	0.1592	5082	X-RAY DIFFRACTION	99.83
2.19-2.42	0.2077	143	0.1539	5042	X-RAY DIFFRACTION	99.79
2.42-2.77	0.1849	146	0.1675	5124	X-RAY DIFFRACTION	99.94
2.77-3.48	0.1877	145	0.1617	5129	X-RAY DIFFRACTION	99.75

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	2.54665419477	0.693044828377	0.299305788263	2.81374027161	-0.171930203262	1.83662623469	0.0764965840153	0.409791840823	0.376858322606	-0.164988471845	0.107461199553	-0.0134946335514	-0.093541336685	0.0108691950655	-0.173971632476	0.0975089886109	0.00711863601581	0.0260738014567	0.123140776734	0.0425630803036	0.109295089215	-19.965382248	9.43983649721	-13.2655016886
2	2.40859013374	0.28487434888	-0.536351322107	1.01680419453	-0.0754942483816	2.39184014616	0.0710212735762	0.077637193107	0.217726049521	0.00976952250408	0.014907687281	0.0817745002935	-0.108424779981	-0.0650490851961	-0.0373399909035	0.0908725346539	-0.00176833493087	0.0124345880725	0.0907152126259	-0.000514254529797	0.0811399562673	-26.9220869652	2.45623780647	-5.30919200107
3	1.71179411728	0.343309294056	-0.336783484867	0.918948150706	0.23426163789	2.48159477256	0.0223015464627	-0.220914946135	-0.111550538877	0.0631473854446	-0.0297175812323	-0.03665869203	0.100601388602	-0.0450837896268	0.0129970023527	0.087178940131	0.000941730759922	0.000460581168789	0.0934106965656	0.00895365707729	0.0482004909525	-21.5792060649	-4.96658648944	1.71315066648
4	2.29344993011	-0.342099068099	0.157067682504	1.89526137304	-0.0570121589515	2.42450883336	0.114885216622	-0.412974615129	0.0566424678311	0.102697492858	-0.108738315353	0.0540377971991	-0.0191830922479	0.156022087214	-0.0290921058945	0.0737618856544	-0.0230372487862	-0.00585156255064	0.150747041024	-0.0342563670761	0.108664719391	-6.22530972385	2.19674552161	0.94348378142
5	2.12340119388	0.122531191986	-0.184887604968	2.95014038503	-0.403133199148	1.3824524275	0.0414488066484	0.0120039730278	0.0448514061843	-0.093790663264	-0.0126548791894	-0.24020226977	0.00132936770322	0.138913579007	-0.053485276361	0.0697541065418	7.59466241288E-5	0.0176546360253	0.114127251306	-0.0231424869387	0.0803741120273	-9.32234431729	1.82731921873	-5.125860728
6	3.69587889259	-0.493565766765	0.748530655606	4.44461885975	0.592883212748	1.71164259537	-0.0171418500749	-0.0710394282396	-0.163939394427	0.0352947605362	-0.0474138424866	0.19079435142	0.0120875066637	0.0858006023633	0.00560311520363	0.126993621311	0.00540246748543	0.00551316996533	0.0910579376184	0.045045851913	0.231864054171	-35.1882973583	-32.5881361525	3.49803753713
7	3.66365370001	-2.25230548272	1.01236395942	3.97369974271	0.0839755279035	2.17634315152	0.201141728654	0.489406782599	-0.0437542843748	-0.862276553772	-0.270044065276	0.461344851436	-0.134924933639	0.112965052525	0.0403595729905	0.27846824	0.0162151360242	-0.0728847340402	0.164885483962	0.0464256581966	0.368281676703	-41.0066956015	-31.3048914703	-4.4453250388
8	0.248147125211	-0.8967810781	-0.30502096334	3.0925678919	0.858869450554	0.211876452154	0.0308709942801	-0.155073638146	-0.540701164228	-0.30178832351	-0.0851151941889	0.61399782832	0.0134633178584	-0.124819739203	-0.00288650994305	0.149956638833	-0.0197613479009	-0.00467689055844	0.0924899702779	0.0828967526714	0.453390232343	-45.7778143574	-24.2560681654	3.47350018361
9	0.678011759181	1.86217914395	-0.583387280648	5.42745639321	-1.26475513674	1.17395751152	-0.0447623684611	-0.296626018653	-0.49992954391	0.227582200992	-0.0727904163934	0.78434011367	-0.0394175036568	-0.195628119417	-0.0460510436836	0.123944899866	-0.0142837863342	0.0700458323027	0.202438828299	0.107079308956	0.546492903242	-51.2436768359	-26.1717537237	9.20079254948
10	0.889451400735	0.172383894819	-0.452038064542	4.30595112479	-0.360087655989	0.475085827832	-0.0324800650293	-0.543404818049	-0.268880624123	0.675052457951	0.00395082336118	0.0751117546931	-0.00180229765787	0.115259455065	0.0919495610754	0.205359926558	-0.0223279459637	0.00545119402987	0.243457962443	0.0996340206536	0.199978709344	-37.9745586318	-16.5551818622	14.6534226055
11	2.78742641004	1.74053793243	-1.2106385203	7.4958906987	-0.739500660372	1.16051050788	-0.0556898081113	-0.33026875536	-0.23146959147	0.276778286066	-0.00663008265671	0.239985417751	0.0839368554611	0.134340631866	0.0223156209259	0.134917058679	-0.00106833050722	0.0147277954409	0.238614719333	0.0546083575556	0.175760279909	-44.4159841535	-13.8747916951	12.4977641078
12	2.57204583678	0.179954810197	-1.6514204336	2.84068778198	0.296289785517	3.66092793496	0.0128479991878	-0.408651411568	-0.171668281883	0.178870525115	0.259046331244	0.117255587307	-0.253717052746	0.213619865648	-0.100815296926	0.199269215245	-0.0037053815336	0.0528489926471	0.211012672587	0.110402007321	0.19882290549	-36.4164593403	-22.3391206772	13.7441822308
13	3.9037882976	-0.962195940199	-3.06073491732	3.0342710874	0.809891527387	5.82511402088	0.144161636124	-0.961642232539	0.388584794165	0.264238017477	0.187889065702	-0.49902112598	-0.652179227075	0.826265139096	-0.338008912698	0.217758074754	-0.0561863955395	-0.0498433537387	0.550424703437	-0.000413321932734	0.28002759404	-24.6582716595	-20.7418559881	14.2098544901
14	3.23440966483	0.707922902397	-2.56636611243	4.66788749043	-0.644320591803	4.39811409068	0.0265142013584	-0.495502339101	-0.218393480928	0.154089566374	0.0193869021405	-0.0855793519207	0.118084454159	0.687832607353	-0.0521967662664	0.139023660249	-0.00864881425319	-0.0200831627872	0.248512697184	0.0662419639186	0.23624086728	-28.9948546436	-27.4421485669	9.72596911983
15	1.96630910736	-0.799182484614	-1.72178991042	4.56269403333	0.238273201419	4.53353593171	-0.0408098562741	-0.535549520111	-0.231795551347	0.455889793486	0.314949757953	-0.412314273472	-0.0657373858075	0.695888101075	0.059074524882	0.194492327236	0.00269640848309	-0.0545674901554	0.457800943451	0.101092788903	0.217979339559	-28.3992132284	-24.2349130671	16.8456002605

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 0 through 34 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 35 through 122 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 123 through 155 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 156 through 174 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 175 through 206 )
6	X-RAY DIFFRACTION	6	chain 'B' and (resid 1 through 26 )
7	X-RAY DIFFRACTION	7	chain 'B' and (resid 27 through 57 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 58 through 85 )
9	X-RAY DIFFRACTION	9	chain 'B' and (resid 86 through 101 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 102 through 122 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 123 through 142 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 143 through 155 )
13	X-RAY DIFFRACTION	13	chain 'B' and (resid 156 through 174 )
14	X-RAY DIFFRACTION	14	chain 'B' and (resid 175 through 190 )
15	X-RAY DIFFRACTION	15	chain 'B' and (resid 191 through 206 )

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