PDB-7a1s: FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH ZN(II), 3-methyl-2-...

ID or keywords:

Entry

Database: PDB / ID: 7a1s

Title

FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH ZN(II), 3-methyl-2-oxoglutarate, AND TANKYRASE-2 (TNKS2) FRAGMENT PEPTIDE (21-MER)

Components

Hypoxia-inducible factor 1-alpha inhibitor
TANKYRASE-2

Keywords

OXIDOREDUCTASE / Hypoxia-inducible factor asparagine hydroxylase / Dioxygenase

Function / homology

Function and homology information

hypoxia-inducible factor-asparagine dioxygenase / : / [protein]-asparagine 3-dioxygenase activity / peptidyl-histidine dioxygenase activity / peptidyl-aspartic acid 3-dioxygenase activity / Cellular response to hypoxia / carboxylic acid binding / positive regulation of vasculogenesis / ankyrin repeat binding / oxygen sensor activity ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.01 Å

Authors

Nakashima, Y. / Brewitz, L. / Schofield, C.J.

Citation

Journal: Nat Commun / Year: 2021
Title: 2-Oxoglutarate derivatives can selectively enhance or inhibit the activity of human oxygenases.
Authors: Nakashima, Y. / Brewitz, L. / Tumber, A. / Salah, E. / Schofield, C.J.

History

Deposition	Aug 13, 2020	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Aug 25, 2021	Provider: repository / Type: Initial release
Revision 1.1	Dec 22, 2021	Group: Database references / Category: citation / citation_author Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2	Jan 31, 2024	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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PDBx/mmCIF format	7a1s.cif.gz	274.7 KB	Display	PDBx/mmCIF format
PDB format	pdb7a1s.ent.gz	186.8 KB	Display	PDB format
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Validation report

Summary document	7a1s_validation.pdf.gz	354.2 KB	Display	wwPDB validaton report
Full document	7a1s_full_validation.pdf.gz	354.9 KB	Display
Data in XML	7a1s_validation.xml.gz	18.2 KB	Display
Data in CIF	7a1s_validation.cif.gz	27 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/a1/7a1s ftp://data.pdbj.org/pub/pdb/validation_reports/a1/7a1s	HTTPS FTP

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Related structure data

Related structure data	7a1jC 7a1kC 7a1lC 7a1mC 7a1nC 7a1oC 7a1pC 7a1qC 1h2kS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	7a1j-d 3p3p-d 5jwl-d 7a1n-d 7a1p-d 6h9j-d 6hl6-d 3od4-d 6hl5-d 1mzf-d 3kcy-d 5op6-d 7a1q-d 2wa3-d 4nr1-d 4ai8-d 1yci-d 5jwp-d 1mze-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	#240 - Dec 2019 Hypoxia-Inducible Factors similarity (10) #122 - Feb 2010 Enhanceosome similarity (1)

Deposited unit

A: Hypoxia-inducible factor 1-alpha inhibitor

B: TANKYRASE-2

hetero molecules

43.6 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)	86.089, 86.089, 148.417
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	92
Space group name H-M	P4₁2₁2
Space group name Hall	P4abw2nw
Symmetry operation	#1: x,y,z #2: -y+1/2,x+1/2,z+1/4 #3: y+1/2,-x+1/2,z+3/4 #4: x+1/2,-y+1/2,-z+3/4 #5: -x+1/2,y+1/2,-z+1/4 #6: -x,-y,z+1/2 #7: y,x,-z #8: -y,-x,-z+1/2

Components on special symmetry positions

ID	Model	Components
1	1	B-824- HOH

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Protein / Protein/peptide , 2 types, 2 molecules AB

#1: Protein	Hypoxia-inducible factor 1-alpha inhibitor / Factor inhibiting HIF-1 / FIH-1 / Hypoxia-inducible factor asparagine hydroxylase Mass: 40328.281 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HIF1AN, FIH1 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q9NWT6, hypoxia-inducible factor-asparagine dioxygenase, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one ...References: UniProt: Q9NWT6, hypoxia-inducible factor-asparagine dioxygenase, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor
#2: Protein/peptide	TANKYRASE-2 Mass: 2229.402 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)

#1: Protein

Hypoxia-inducible factor 1-alpha inhibitor / Factor inhibiting HIF-1 / FIH-1 / Hypoxia-inducible factor asparagine hydroxylase

Mass: 40328.281 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Gene: HIF1AN, FIH1 / Production host:

Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9NWT6, hypoxia-inducible factor-asparagine dioxygenase, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one ...

#2: Protein/peptide

TANKYRASE-2

Mass: 2229.402 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.)

Homo sapiens (human)

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Non-polymers , 4 types, 317 molecules

#3: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: SO₄
#4: Chemical	ChemComp-ROQ / (3~{S})-3-methyl-2-oxidanylidene-pentanedioic acid Mass: 160.125 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₆H₈O₅ / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 307 / Source method: isolated from a natural source / Formula: H₂O

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Details

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: 3.23 Å³/Da / Density % sol: 61.93 %
Crystal grow	Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 1.6M AMMONIUM SULPHATE, 6% PEG 400, 0.1M HEPES PH 7.5

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97933 Å
Detector	Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Jul 20, 2019
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97933 Å / Relative weight: 1
Reflection	Resolution: 2.006→74.47 Å / Num. obs: 38135 / % possible obs: 100 % / Redundancy: 25.8 % / B_iso Wilson estimate: 45.92 Å² / CC_1/2: 0.999 / R_merge(I) obs: 0.219 / Net I/σ(I): 13.5
Reflection shell	Resolution: 2.006→2.04 Å / Redundancy: 27.8 % / Mean I/σ(I) obs: 0.5 / Num. unique obs: 1861 / CC_1/2: 0.351 / % possible all: 100

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Processing

Software

Name	Version	Classification
PHENIX	1.17.1_3660	refinement
XDS		data reduction
PHASER		phasing
autoPROC		data scaling

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 1H2K

1h2k

Resolution: 2.01→74.47 Å / SU ML: 0.2295 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 21.5717
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.2089	1901	5.01 %
R_work	0.1804	36065	-
obs	0.1818	37966	99.55 %

Solvent computation

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

Displacement parameters

B_iso mean: 59.46 Å²

Refinement step

Cycle: LAST / Resolution: 2.01→74.47 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2870	0	40	312	3222

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0022	3012
X-RAY DIFFRACTION	f_angle_d	0.5132	4104
X-RAY DIFFRACTION	f_chiral_restr	0.0424	412
X-RAY DIFFRACTION	f_plane_restr	0.0032	544
X-RAY DIFFRACTION	f_dihedral_angle_d	16.783	1101

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 (%)
2.01-2.06	0.3345	132	0.3326	2381	X-RAY DIFFRACTION	94.58
2.06-2.11	0.3451	141	0.2963	2517	X-RAY DIFFRACTION	99.51
2.11-2.17	0.2793	118	0.279	2557	X-RAY DIFFRACTION	99.81
2.17-2.24	0.2855	145	0.2473	2516	X-RAY DIFFRACTION	100
2.24-2.32	0.2279	137	0.2337	2564	X-RAY DIFFRACTION	100
2.32-2.42	0.2221	134	0.2216	2540	X-RAY DIFFRACTION	100
2.42-2.53	0.2277	152	0.205	2569	X-RAY DIFFRACTION	99.96
2.53-2.66	0.2324	127	0.2043	2543	X-RAY DIFFRACTION	99.96
2.66-2.83	0.2462	140	0.2054	2582	X-RAY DIFFRACTION	99.96
2.83-3.05	0.2168	117	0.1952	2605	X-RAY DIFFRACTION	99.96
3.05-3.35	0.2055	144	0.1822	2586	X-RAY DIFFRACTION	100
3.35-3.84	0.1798	129	0.1536	2626	X-RAY DIFFRACTION	99.96
3.84-4.83	0.1672	132	0.1251	2672	X-RAY DIFFRACTION	100
4.83-74.47	0.2067	153	0.1835	2807	X-RAY DIFFRACTION	99.9

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	0.07900996937	-0.235957618766	0.124040217114	0.945476420458	-0.22332532548	0.277193671099	-0.106306934566	0.487892180905	-0.649349989001	-0.265384540585	-0.203555889547	-0.156414174039	0.444745944992	0.0704739216034	0.285979017926	0.546050855741	0.026490728583	0.0398100898169	0.744293603611	-0.210069393457	0.695179909498	-29.5090833859	10.4283985429	-22.7498722114
2	2.11125179454	0.211917715724	-1.36075737654	1.6402000637	0.134913197748	1.9955730548	-0.0952223742824	-0.12070918505	-0.142182808648	0.188437605202	0.0732091982958	-0.241423034491	0.00678711984473	0.305443072341	0.0287301535111	0.354243232121	0.0754912296352	-0.0304429242544	0.531241306924	-0.098780102739	0.467977958234	-16.4017965486	19.0293000883	-14.7340021573
3	2.2651367609	-0.741222446492	-0.480925711	5.70098714956	1.54696548151	2.56333122376	-0.324286405271	-0.413359711743	0.072516495447	1.29362890331	0.100990823891	0.223209995337	0.338100506114	0.00175207448618	0.170651056434	0.702317802764	0.0399450887793	0.00898737423117	0.728096118637	-0.0222933724266	0.564430566322	-31.5602667237	20.492344933	6.47780141031
4	4.18249543044	-0.457361284856	-0.814331736311	0.529252992253	-0.432165700302	1.56762255333	-0.312960640389	-1.06189493434	-0.656821767957	0.64235924033	0.278480893882	-0.0270811682149	0.704229456809	0.750962745683	-0.0254392070027	0.817287709471	0.257129875642	-0.0642407495878	0.923457077107	0.0798916159696	0.60829486255	-15.3373937733	8.41431302877	3.75890470682
5	2.14227487694	-0.56796886826	-0.391707045907	0.595876791982	0.343221324669	2.56509551494	-0.084784737099	-0.52998309366	-0.210420602248	0.273800126638	0.0359228265881	-0.229447187227	0.163447728689	0.651753682879	0.0709013078019	0.38220250726	0.122866413575	-0.072207291463	0.67472644053	-0.0348895135525	0.471819728262	-12.7906032545	16.4535985323	-5.52656332817
6	2.4585328151	-0.788444205494	-0.828114761501	2.23131055477	-0.00915658579842	1.65162424876	0.27666011682	-0.160796803401	0.451317457411	0.071112203427	-0.0385528077257	-0.214569798977	-0.26703479364	0.463165872919	-0.274946745332	0.352941063793	-0.00779812633755	0.0206021430293	0.539003189237	-0.0616861037432	0.470418585452	-16.8104922242	29.5538674497	-15.9118849938
7	2.41404509469	-0.644766456496	-1.00400691156	0.935529891742	0.341159304161	1.81034370588	-0.00901035711698	0.0409422733144	-0.221543949155	0.114113142788	-0.0212560553236	0.0305219286457	0.107200018796	-0.000574430646938	0.0204513493808	0.338790505094	0.0133022629126	-0.00938831098758	0.480750443929	-0.0667093689071	0.42685487243	-32.5927666846	19.9968662056	-10.1144277581
8	2.84988744959	-0.49050587657	-0.209617254387	1.97593686557	0.175621485592	0.929319076935	0.130033999502	0.0988579082199	0.543574023577	-0.22242820627	-0.00708082390309	-0.266124845553	-0.549364157553	0.300343792371	-0.101452376653	0.481331783828	-0.00438121307821	0.0871103688283	0.469451121697	-0.0429069563739	0.522382595214	-36.2104651889	40.8320393416	-8.43651129385
9	7.07161142655	-1.53008311612	1.81506349622	3.0990934395	-1.08178383271	3.1967315633	0.0957450760082	-0.536774206485	-0.331325424213	0.161737967571	0.0870487877555	0.0324336559316	-0.0107561014653	0.235598165401	-0.181019053359	0.501577434931	-0.0097967318105	0.0770571162242	0.463730050523	-0.0276740817517	0.391307090526	-49.1707154679	37.5671802037	5.50491916534
10	8.06781945137	-0.817428229478	1.60477660571	8.91139944755	0.717587134091	7.75244400655	0.325127546187	0.507052996842	1.54916704228	-0.460638136146	0.159788618562	-1.11128519455	-1.52647079379	0.838317612281	-0.263738689678	0.833665823574	-0.124487856437	0.266924769475	0.738647103503	-0.052140279581	0.939509274549	-35.6094682242	49.3037991118	-6.71904750851
11	5.34810546024	-1.71130387243	-0.259514694323	4.37628836048	0.913257649332	1.43139241159	-0.000554371226386	-0.680608066505	0.484508757064	0.0522010784445	0.191855519057	-0.699903608252	-0.349314810752	0.269924300876	-0.138630025738	0.457757796996	0.0155093990584	-0.00789262859471	0.635628253772	-0.0966870455379	0.462617393628	-27.3795024077	33.581561373	-4.29425727319

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 15 through 49 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 50 through 95 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 96 through 117 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 118 through 137 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 138 through 166 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 167 through 190 )
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 191 through 297 )
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 298 through 329 )
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 330 through 349 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 692 through 698 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 699 through 708 )

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