PDB-5lat: HIF prolyl hydroxylase 2 (PHD2/EGLN1) P317R variant in complex wi...

ID or keywords:

Entry

Database: PDB / ID: 5lat

Title

HIF prolyl hydroxylase 2 (PHD2/EGLN1) P317R variant in complex with Mn(II) and N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]glycine (IOX3/UN9)

Components

Egl nine homolog 1

Keywords

OXIDOREDUCTASE / NON-HEME DIOXYGENASE / IRON / 2-OXOGLUTARATE / HYPOXIA-INDUCIBLE FACTOR / HIF / HIF PROLYL HYDROXYLASE DOMAIN 2 / PHD2 / EGLN1 / OXYGENASE / HYPOXIA / DNA-BINDING / METAL-BINDING / TRANSCRIPTION / HELIX-LOOP-HELIX-BETA / DSBH / FACIAL TRIAD / CYTOPLASM / TRANSCRIPTION/EPIGENETIC REGULATION / SIGNALING / DEVELOPMENT / CELL STRUCTURE / BETA-HYDROXYLATION / TRANSCRIPTION ACTIVATOR/INHIBITOR / UBL CONJUGATION / POLYMORPHISM / VITAMIN C / ZINC-FINGER / FAMILIAL ERYTHROCYTOSIS / BREAST CANCER / TRANSCRIPTION COMPLEX

Function / homology

Function and homology information

hypoxia-inducible factor-proline dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / peptidyl-proline 4-dioxygenase activity / peptidyl-proline dioxygenase activity / peptidyl-proline hydroxylation to 4-hydroxy-L-proline / negative regulation of cyclic-nucleotide phosphodiesterase activity / regulation protein catabolic process at postsynapse / intracellular oxygen homeostasis / labyrinthine layer development / cardiac muscle tissue morphogenesis ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.9 Å

Authors

Chowdhury, R. / Schofield, C.J.

Citation

Journal: Nat Commun / Year: 2016
Title: Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases.
Authors: Chowdhury, R. / Leung, I.K. / Tian, Y.M. / Abboud, M.I. / Ge, W. / Domene, C. / Cantrelle, F.X. / Landrieu, I. / Hardy, A.P. / Pugh, C.W. / Ratcliffe, P.J. / Claridge, T.D. / Schofield, C.J.

History

Deposition	Jun 15, 2016	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Aug 31, 2016	Provider: repository / Type: Initial release
Revision 1.1	Sep 7, 2016	Group: Database references
Revision 1.2	Nov 29, 2017	Group: Database references / Category: pdbx_database_related
Revision 1.3	Jan 10, 2024	Group: Data collection / Database references / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	5lat.cif.gz	149.3 KB	Display	PDBx/mmCIF format
PDB format	pdb5lat.ent.gz	118.4 KB	Display	PDB format
PDBx/mmJSON format	5lat.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	5lat_validation.pdf.gz	736 KB	Display	wwPDB validaton report
Full document	5lat_full_validation.pdf.gz	736.9 KB	Display
Data in XML	5lat_validation.xml.gz	12.8 KB	Display
Data in CIF	5lat_validation.cif.gz	18.2 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/la/5lat ftp://data.pdbj.org/pub/pdb/validation_reports/la/5lat	HTTPS FTP

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Related structure data

Related structure data	5l9bC 5l9rC 5l9vC 5la9C 5lasC 5lb6C 5lbbC 5lbcC 5lbeC 5lbfC 4bqxS 3hqr S: Starting model for refinement C: citing same article (ref.)
Similar structure data	5lb6-d 6yw0-d 5ox5-d 5lbc-d 2z43-1 6yvz-d 6yvx-d 6yvw-d 5lbb-d 5ox6-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 (12) #244 - Apr 2020 Photosynthetic Supercomplexes similarity (1) #49 - Jan 2004 Carbonic Anhydrase similarity (1) #59 - Nov 2004 Photosystem II similarity (1)

Deposited unit

A: Egl nine homolog 1

hetero molecules

28.6 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	111.182, 111.182, 40.028
Angle α, β, γ (deg.)	90.00, 90.00, 120.00
Int Tables number	173
Space group name H-M	P6₃

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Protein , 1 types, 1 molecules A

#1: Protein	Egl nine homolog 1 / Hypoxia-inducible factor prolyl hydroxylase 2 / HPH-2 / Prolyl hydroxylase domain-containing ...Hypoxia-inducible factor prolyl hydroxylase 2 / HPH-2 / Prolyl hydroxylase domain-containing protein 2 / PHD2 / SM-20 Mass: 28157.020 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, UNP residues 181-426 / Mutation: P317R Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EGLN1, C1orf12, PNAS-118, PNAS-137 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q9GZT9, hypoxia-inducible factor-proline dioxygenase

#1: Protein

Egl nine homolog 1 / Hypoxia-inducible factor prolyl hydroxylase 2 / HPH-2 / Prolyl hydroxylase domain-containing ...

Mass: 28157.020 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, UNP residues 181-426 / Mutation: P317R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Gene: EGLN1, C1orf12, PNAS-118, PNAS-137 / Production host:

Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9GZT9, hypoxia-inducible factor-proline dioxygenase

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Non-polymers , 5 types, 190 molecules

#2: Chemical	ChemComp-MN / MANGANESE (II) ION Mass: 54.938 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mn
#3: Chemical	ChemComp-UN9 / N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE Mass: 280.664 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₂H₉ClN₂O₄
#4: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃H₈O₃
#5: Chemical	ChemComp-BCT / BICARBONATE ION Mass: 61.017 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: CHO₃ / Comment: pH buffer*YM
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 186 / 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: 2.87 Å³/Da / Density % sol: 57.19 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 5.6 Details: 0.1 M tri-sodium citrate pH 5.6, 20% PEG 4000, 20% 2-propanol

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
Detector	Type: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 29, 2007 / Details: MIRRORS
Radiation	Monochromator: SI 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9795 Å / Relative weight: 1
Reflection	Resolution: 1.9→27.8 Å / Num. obs: 22463 / % possible obs: 99.6 % / Redundancy: 2.8 % / B_iso Wilson estimate: 21.36 Å² / CC_1/2: 0.991 / R_merge(I) obs: 0.088 / Net I/σ(I): 9.1
Reflection shell	Resolution: 1.9→2 Å / Redundancy: 2.9 % / R_merge(I) obs: 0.354 / Mean I/σ(I) obs: 2.9 / % possible all: 99.8

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Processing

Software

Name	Version	Classification
PHENIX	(1.10_2155: ???)	refinement
MOSFLM		data reduction
SCALA		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4BQX

4bqx

Resolution: 1.9→27.796 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 16.09 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.1659	1149	5.12 %
R_work	0.1504	-	-
obs	0.1512	22455	99.49 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT MODEL / B_sol: 68.8 Å² / k_sol: 0.42 e/Å³

Displacement parameters

B_iso mean: 33 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-2.87 Å²	0 Å²	0 Å²
2-	-	-2.87 Å²	0 Å²
3-	-	-	5.75 Å²

Refine analyze

	Free	Obs
Luzzati coordinate error	0.25 Å	0.23 Å
Luzzati d res low	-	5 Å
Luzzati sigma a	-	0.24 Å

Refinement step

Cycle: LAST / Resolution: 1.9→27.796 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1718	0	30	186	1934

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.006	1838
X-RAY DIFFRACTION	f_angle_d	0.852	2491
X-RAY DIFFRACTION	f_dihedral_angle_d	14.477	1096
X-RAY DIFFRACTION	f_chiral_restr	0.052	261
X-RAY DIFFRACTION	f_plane_restr	0.005	328

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 (%)
1.9001-1.9866	0.2436	147	0.203	2648	X-RAY DIFFRACTION	100
1.9866-2.0913	0.2122	152	0.1718	2613	X-RAY DIFFRACTION	100
2.0913-2.2223	0.1859	144	0.1501	2670	X-RAY DIFFRACTION	100
2.2223-2.3938	0.164	146	0.1474	2622	X-RAY DIFFRACTION	100
2.3938-2.6345	0.1855	153	0.1416	2685	X-RAY DIFFRACTION	100
2.6345-3.0153	0.1742	139	0.1382	2660	X-RAY DIFFRACTION	100
3.0153-3.7974	0.1405	133	0.1372	2659	X-RAY DIFFRACTION	99
3.7974-27.7985	0.1399	135	0.1551	2749	X-RAY DIFFRACTION	99

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	0.177	-0.1492	-0.0965	0.3915	0.2453	0.1513	0.0232	0.0135	-0.1767	-0.0376	-0.0415	0.4236	-0.2139	-0.0463	0.0101	0.194	-0.0417	0.0709	0.2217	0.0549	0.3657	21.0757	-31.7969	2.0936
2	0.6159	-0.6461	0.5305	0.7273	-0.3743	1.4786	0.2336	0.0797	0.017	-0.0142	0.1046	0.3007	0.023	-0.1541	0.3006	0.1044	-0.0267	0.098	0.1904	0.0269	0.3004	24.4638	-23.3744	0.5152
3	0.1736	-0.0327	0.182	0.1572	-0.145	0.4189	-0.0802	-0.2442	0.2262	0.2251	0.0582	0.13	-0.3482	-0.1791	0.0017	0.3496	0.0372	0.1512	0.1888	-0.0805	0.243	33.9237	-9.5908	12.1127
4	1.1962	-0.4386	0.2513	0.6887	0.1301	0.498	-0.0136	0.0933	0.3533	0.3328	-0.0962	-0.296	-0.0405	0.1384	-0.148	0.1879	-0.0109	-0.0041	0.1406	0.0094	0.1709	48.6256	-11.7166	2.5278
5	0.5531	-0.3275	0.1905	0.232	-0.038	0.2077	0.0542	-0.2716	-0.1187	0.3904	0.056	0.2744	-0.1615	-0.1032	0.3353	0.2734	-0.0677	0.2751	0.1638	0.1155	0.1214	31.0215	-26.6415	11.949
6	0.0162	-0.0049	0.0345	0.0013	-0.0097	0.0771	0.1062	0.1008	-0.1721	0.0551	-0.0326	0.271	0.1716	0.1321	0.0004	0.1869	0.0083	0.0204	0.1681	0.0378	0.328	31.801	-39.7742	3.2169
7	0.2976	0.0242	-0.0019	0.003	0.0015	0.0017	0.0795	-0.0668	0.197	0.0787	-0.0887	-0.0279	-0.0439	0.004	-0.0005	0.1883	-0.0129	0.0176	0.0985	0.0356	0.1095	41.2258	-17.4495	3.1982
8	0.1515	0.0728	0.0086	0.1075	0.0105	0.0713	-0.0211	0.1219	-0.0776	-0.2668	-0.096	-0.2437	0.0658	0.0688	-0.0287	0.1764	0.0135	0.0676	0.1314	0.0154	0.1376	43.5606	-24.6864	-8.5815
9	0.2941	-0.0019	0.0153	0.0128	0.0553	0.3943	0.0553	0.0712	0.1646	0.0341	-0.0009	0.2383	0.012	-0.1757	0.1057	0.1052	0.0323	0.0803	0.1092	0.0466	0.2134	32.2107	-17.7543	0.9072
10	0.2865	0.223	-0.1001	0.1808	-0.087	0.0424	0.0874	0.3896	0.1369	-0.1444	0.0021	0.3296	0.1636	-0.1032	0.0265	0.2367	0.0361	-0.0592	0.2036	0.0211	0.1874	31.9449	-18.1386	-12.0988
11	0.058	0.0823	-0.087	0.1392	-0.1048	0.1264	0.099	0.2905	0.1996	-0.1698	-0.054	0.4145	0.0128	-0.2516	0.0133	0.2153	0.0605	-0.0109	0.2841	0.0226	0.2381	27.6227	-17.1936	-7.3494
12	0.012	0.008	0.0049	0.031	-0.0117	0.0096	0.0849	0.0942	-0.0853	0.0322	-0.0164	0.0697	0.1828	-0.1483	0.0005	0.1738	0.001	0.0195	0.1499	-0.0008	0.1675	32.6984	-28.0094	-4.2146
13	0.125	-0.0106	0.0124	0.007	0.0082	0.0178	-0.0024	0.2287	0.1233	-0.2228	0.0379	0.1044	-0.1527	-0.1053	0.0005	0.1812	0.0013	0.006	0.1432	0.0406	0.1257	36.8976	-15.1536	-9.7289
14	0.0666	-0.0875	0.0755	0.3667	-0.0573	0.1334	-0.0571	-0.035	-0.0817	0.1452	0.123	0.1634	-0.0602	-0.1152	0.0016	0.1202	0.0063	0.0505	0.0726	0.0176	0.1335	37.7264	-22.5503	3.013
15	0.0094	0.003	-0.0059	0.0075	-0.0095	0.0129	0.0565	-0.0167	0.083	-0.0479	-0.0018	-0.0279	0.0136	0.1557	-0.0001	0.182	-0.0159	0.0036	0.1374	0.0086	0.198	48.665	-40.4287	0.345
16	0.0351	-0.0227	0.0093	0.0219	-0.0072	0.0027	0.0035	-0.045	0.0174	0.0359	-0.0462	0.0318	0.0026	0.008	0.0001	0.69	0.0628	-0.1329	0.8677	-0.0777	0.6002	62.6601	-44.0361	11.0366

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	(chain A and resid 188:204)
2	X-RAY DIFFRACTION	2	(chain A and resid 205:215)
3	X-RAY DIFFRACTION	3	(chain A and resid 216:232)
4	X-RAY DIFFRACTION	4	(chain A and resid 233:266)
5	X-RAY DIFFRACTION	5	(chain A and resid 267:283)
6	X-RAY DIFFRACTION	6	(chain A and resid 284:293)
7	X-RAY DIFFRACTION	7	(chain A and resid 294:306)
8	X-RAY DIFFRACTION	8	(chain A and resid 307:320)
9	X-RAY DIFFRACTION	9	(chain A and resid 321:335)
10	X-RAY DIFFRACTION	10	(chain A and resid 336:350)
11	X-RAY DIFFRACTION	11	(chain A and resid 351:361)
12	X-RAY DIFFRACTION	12	(chain A and resid 362:371)
13	X-RAY DIFFRACTION	13	(chain A and resid 372:381)
14	X-RAY DIFFRACTION	14	(chain A and resid 382:392)
15	X-RAY DIFFRACTION	15	(chain A and resid 393:404)
16	X-RAY DIFFRACTION	16	(chain A and resid 408:411)

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