PDB-7a1q: FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH ZN(II), 3-(carboxyc...

ID or keywords:

Entry

Database: PDB / ID: 7a1q

Title

FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH ZN(II), 3-(carboxycarbonyl)cyclopentane-1-carboxylic acid, AND CONSENSUS ANKYRIN REPEAT DOMAIN (20-MER)

Components

CONSENSUS ANKYRIN REPEAT DOMAIN
Hypoxia-inducible factor 1-alpha inhibitor

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)
synthetic construct (others)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.75 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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Download

PDBx/mmCIF format	7a1q.cif.gz	270.5 KB	Display	PDBx/mmCIF format
PDB format	pdb7a1q.ent.gz	184 KB	Display	PDB format
PDBx/mmJSON format	7a1q.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	7a1q_validation.pdf.gz	335.6 KB	Display	wwPDB validaton report
Full document	7a1q_full_validation.pdf.gz	337.6 KB	Display
Data in XML	7a1q_validation.xml.gz	16.9 KB	Display
Data in CIF	7a1q_validation.cif.gz	24 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/a1/7a1q ftp://data.pdbj.org/pub/pdb/validation_reports/a1/7a1q	HTTPS FTP

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Related structure data

Related structure data	7a1jC 7a1kC 7a1lC 7a1mC 7a1nC 7a1oC 7a1pC 7a1sC 1h2kS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	3p3n-1 2ilm-1 5jwk-1 2y0i-1 3p3p-1 1h2k-1 4z2w-1 5op8-1 5jwp-1 7a1p-1 1yci-1 6hkp-1 6ha6-1 4z1v-1 1h2m-1 7a1m-1 5opc-1 7a1o-1 7a1k-1 Search similar-shape structures by Omokage search (details) 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: CONSENSUS ANKYRIN REPEAT DOMAIN

hetero molecules

43 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Hypoxia-inducible factor 1-alpha inhibitor

B: CONSENSUS ANKYRIN REPEAT DOMAIN

hetero molecules

A: Hypoxia-inducible factor 1-alpha inhibitor

B: CONSENSUS ANKYRIN REPEAT DOMAIN

hetero molecules

defined by author&software
Evidence: gel filtration
86.1 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	85.968, 85.968, 148.177
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

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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	CONSENSUS ANKYRIN REPEAT DOMAIN Mass: 2165.465 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

#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

CONSENSUS ANKYRIN REPEAT DOMAIN

Mass: 2165.465 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

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Non-polymers , 4 types, 190 molecules

#3: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#4: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO₄
#5: Chemical	ChemComp-QVQ / 3-(carboxycarbonyl)cyclopentane-1-carboxylic acid / (1~{R},3~{S})-3-(carboxycarbonyl)cyclopentane-1-carboxylic acid Mass: 186.162 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₈H₁₀O₅
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 185 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 3.22 Å³/Da / Density % sol: 61.82 %
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: I04 / Wavelength: 0.9795 Å
Detector	Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 30, 2019
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9795 Å / Relative weight: 1
Reflection	Resolution: 1.75→56.122 Å / Num. obs: 56748 / % possible obs: 100 % / Redundancy: 26.8 % / B_iso Wilson estimate: 42.96 Å² / CC_1/2: 1 / R_merge(I) obs: 0.059 / Net I/σ(I): 26.6
Reflection shell	Resolution: 1.75→1.78 Å / Redundancy: 28.1 % / R_merge(I) obs: 8.138 / Mean I/σ(I) obs: 0.4 / Num. unique obs: 2782 / CC_1/2: 0.437 / % 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: 1.75→56.12 Å / SU ML: 0.2332 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 22.68
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.2002	2766	4.93 %
R_work	0.1772	53291	-
obs	0.1783	56057	98.78 %

Solvent computation

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

Displacement parameters

B_iso mean: 56.11 Å²

Refinement step

Cycle: LAST / Resolution: 1.75→56.12 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2887	0	13	185	3085

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0048	3002
X-RAY DIFFRACTION	f_angle_d	0.8441	4086
X-RAY DIFFRACTION	f_chiral_restr	0.0523	417
X-RAY DIFFRACTION	f_plane_restr	0.0056	543
X-RAY DIFFRACTION	f_dihedral_angle_d	18.5658	1103

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 (%)
1.75-1.78	0.4072	111	0.3908	2042	X-RAY DIFFRACTION	77.39
1.78-1.81	0.4017	133	0.376	2628	X-RAY DIFFRACTION	98.54
1.81-1.85	0.352	129	0.3281	2652	X-RAY DIFFRACTION	99.86
1.85-1.88	0.3436	143	0.2891	2641	X-RAY DIFFRACTION	99.96
1.88-1.93	0.2874	146	0.2676	2656	X-RAY DIFFRACTION	100
1.93-1.97	0.2505	129	0.2218	2656	X-RAY DIFFRACTION	100
1.97-2.02	0.2223	136	0.2144	2659	X-RAY DIFFRACTION	99.93
2.02-2.07	0.2556	123	0.1976	2670	X-RAY DIFFRACTION	99.93
2.07-2.14	0.2156	141	0.1881	2678	X-RAY DIFFRACTION	99.82
2.14-2.2	0.213	155	0.1797	2666	X-RAY DIFFRACTION	99.96
2.2-2.28	0.2246	131	0.1656	2668	X-RAY DIFFRACTION	100
2.28-2.37	0.1712	143	0.1736	2668	X-RAY DIFFRACTION	100
2.37-2.48	0.1862	150	0.1673	2688	X-RAY DIFFRACTION	99.93
2.48-2.61	0.1875	149	0.1694	2678	X-RAY DIFFRACTION	100
2.61-2.78	0.2208	148	0.1812	2692	X-RAY DIFFRACTION	100
2.78-2.99	0.1847	152	0.1858	2701	X-RAY DIFFRACTION	100
2.99-3.29	0.2039	130	0.1781	2750	X-RAY DIFFRACTION	100
3.29-3.77	0.1793	142	0.1633	2744	X-RAY DIFFRACTION	100
3.77-4.75	0.1694	125	0.1381	2805	X-RAY DIFFRACTION	99.97
4.75-56.12	0.211	150	0.1946	2949	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	1.70268913268	1.85743032389	-1.60297113188	5.6792684978	3.70268247795	9.69126620676	-0.411729110756	-1.21030287161	0.0884382958378	1.58146317744	-0.310701212709	1.3079106869	0.136675544957	0.749764852333	0.492033451417	0.746501385228	0.068219937215	0.270898294822	0.676009079596	-0.0701974497804	0.821188149435	4.42863197035	-26.2352479268	23.8593686442
2	1.57349865936	-0.261380223488	-0.220047957584	3.0770993358	1.13964465498	1.76963492164	-0.080454648807	-0.0454593033023	0.0463695968898	0.350175521258	0.000245431130123	0.139009055825	0.0279771366821	-0.110572611949	0.0479645723366	0.537008485134	0.0306211334295	0.110053519934	0.365941705313	0.013431445357	0.446877617111	18.5609287498	-22.1937254486	20.1444125918
3	2.63381150083	-0.932590858201	-0.338124916681	2.67250547658	0.933260836096	2.20615745147	0.0429999248866	0.510053591988	-0.0948666974528	-0.375326331097	-0.118780312352	0.00825683789052	-0.410741056746	-0.406657768414	0.0243747430008	0.658712594368	0.0978044234181	-6.7696962081E-5	0.559148764699	0.020794568168	0.483509560691	15.5536076084	-22.4707106	-1.99531213222
4	4.620118155	-2.32001418782	-0.924442863564	4.754284144	0.742789310742	1.70015146783	0.410227818529	0.920472055935	0.0602659461904	-0.916625339129	-0.528269573616	0.321627151223	-0.683315020803	-0.377566530373	0.114508746143	0.771215633146	0.183890433452	-0.101208143616	0.669290293986	0.0204615681571	0.437124878365	13.7199241997	-21.9133740491	-6.2221914043
5	1.12861615569	0.0954345311692	0.266547769789	2.8362138782	1.30570552809	3.4824131548	0.00821089061774	0.207085633267	0.107737674154	-0.661825134907	-0.0717149035819	0.116765543537	-0.675816213531	-0.257514416709	0.0933962482687	0.665655179818	0.114254329552	0.0620392152498	0.416619424909	0.0487917840345	0.509704729785	16.4287994693	-12.4953891471	5.62538170532
6	4.60459449023	-0.781609022714	0.501192577425	2.69374081852	0.666324794135	1.25526784971	0.0639885474505	-0.154219389817	0.375909427982	-0.0646305384264	0.133287835734	-0.335128227106	-0.225491137887	0.0604265690782	-0.231176434138	0.497329462661	-0.00987852870176	0.0702866048966	0.349172563791	-0.00737001042382	0.454666862399	29.5296756336	-16.7367627698	15.9195421352
7	0.835935621538	-0.395277054257	-0.0130183053562	2.36270185122	0.774317272754	1.47409306349	0.0405409160472	0.0727015668675	0.00641070242668	0.0397784087751	-0.0255994798862	0.247147022647	-0.0395046294822	-0.127888663572	-0.0169608173304	0.503283059264	0.0140718765514	0.0736248282197	0.369896156726	0.0132477365872	0.458341216907	19.9273555117	-32.5239955188	10.0312102055
8	2.12183525001	-0.487103331625	0.079121961088	2.58083388576	0.781845793066	1.54494318597	0.054665442177	-0.187447830811	0.111337416703	0.094926141598	0.233261881032	-0.288263916065	0.0192770017285	0.296869978346	-0.290228121913	0.47518463482	0.0182423475015	0.044203242115	0.449645198889	-0.0502554361209	0.516808427038	40.6396692616	-36.2397045604	8.04836797834
9	2.61062283757	-1.33635759559	1.16453678647	3.11798913957	-3.87672062838	4.95359276235	0.0273810794387	0.292253468778	-0.0903411275785	-0.290642167883	0.0911648090462	0.16365236922	-0.0380853608249	-0.157545553797	-0.106618389665	0.481631365875	0.0184767885003	0.0356101599829	0.520537097074	-0.0824662434541	0.411500456138	37.7068393993	-49.2989203408	-5.33064515176
10	2.08476398214	1.8786767125	-0.0191658434604	9.7424238082	-4.50411411037	6.82549670426	0.479643193424	0.215928461431	0.551157746372	0.608241503407	-0.0138376334415	-0.998250239641	-0.142965438949	0.702886381591	-0.483281605597	0.572700304471	-0.0167174635891	-0.0133826516837	0.533038774996	-0.121777829592	0.713556771166	47.562502082	-35.6530872676	6.86929822322
11	7.56640842261	-5.34734918658	3.86285148818	8.17770688376	-1.45194479281	6.5860062154	-0.441122185229	0.927245205587	1.03739812088	-0.633376325652	-0.0149099551974	-0.619071564422	-0.675547682317	0.26799504804	0.497286908436	0.587742518447	-0.0460508645342	0.106176867677	0.392332836311	0.0752831669054	0.535139567763	31.1938762447	-25.2919198559	1.64509838778

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 12 through 31 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 32 through 84 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 85 through 104 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 105 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 3 through 9 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 10 through 20 )

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