PDB-4hwr: Crystal structure of E. coli Threonyl-tRNA synthetase bound to a ...

ID or keywords:

Entry

Database: PDB / ID: 4hwr

Title

Crystal structure of E. coli Threonyl-tRNA synthetase bound to a novel inhibitor

Components

Threonine--tRNA ligase

Keywords

Ligase/Ligase Inhibitor / aminoacyl-tRNA synthetase / protein-inhibitor complex / antibacterial / Ligase-Ligase Inhibitor complex

Function / homology

Function and homology information

tRNA aminoacylation / aminoacyl-tRNA ligase activity / threonine-tRNA ligase / threonyl-tRNA aminoacylation / threonine-tRNA ligase activity / tRNA aminoacylation for protein translation / aminoacyl-tRNA editing activity / negative regulation of translational initiation / mRNA regulatory element binding translation repressor activity / mRNA 5'-UTR binding ...
Similarity search - Function

Biological species

Escherichia coli (E. coli)

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 1.9 Å

Authors

Hilgers, M.T.

Citation

Journal: J.Med.Chem. / Year: 2013
Title: Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design.
Authors: Teng, M. / Hilgers, M.T. / Cunningham, M.L. / Borchardt, A. / Locke, J.B. / Abraham, S. / Haley, G. / Kwan, B.P. / Hall, C. / Hough, G.W. / Shaw, K.J. / Finn, J.

History

Deposition	Nov 8, 2012	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Sep 18, 2013	Provider: repository / Type: Initial release
Revision 1.1	Feb 28, 2024	Group: Data collection / Database references / Derived calculations Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	4hwr.cif.gz	338.2 KB	Display	PDBx/mmCIF format
PDB format	pdb4hwr.ent.gz	276.6 KB	Display	PDB format
PDBx/mmJSON format	4hwr.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	4hwr_validation.pdf.gz	1011.5 KB	Display	wwPDB validaton report
Full document	4hwr_full_validation.pdf.gz	1 MB	Display
Data in XML	4hwr_validation.xml.gz	20.3 KB	Display
Data in CIF	4hwr_validation.cif.gz	31.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/hw/4hwr ftp://data.pdbj.org/pub/pdb/validation_reports/hw/4hwr	HTTPS FTP

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Related structure data

Related structure data	4hwoC 4hwpC 4hwsC 4hwtC C: citing same article (ref.)
Similar structure data	1evl-1 7cbg-d 6l2q-d 4hws-d 7cbi-d 4hwo-d 1fyf-d 4hwp-d 7cbh-d 6l2p-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	#16 - Apr 2001 Aminoacyl-tRNA Synthetases similarity (22) #117 - Sep 2009 Xanthine Oxidoreductase similarity (1) #154 - Oct 2012 Citric Acid Cycle similarity (1) #82 - Oct 2006 Cytochrome p450 similarity (1) #241 - Jan 2020 Twenty Years of Molecules similarity (1)

Deposited unit

A: Threonine--tRNA ligase

B: Threonine--tRNA ligase

hetero molecules

96.9 kDa, 2 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)	156.899, 109.777, 86.995
Angle α, β, γ (deg.)	90.000, 123.760, 90.000
Int Tables number	5
Space group name H-M	C121

Components on special symmetry positions

ID	Model	Components
1	1	A-966- HOH

#1: Protein	Threonine--tRNA ligase / Threonyl-tRNA synthetase / ThrRS Mass: 47998.594 Da / Num. of mol.: 2 / Fragment: UNP residues 242-642 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli (E. coli) / Strain: K12 / Gene: thrS, b1719, JW1709 / Plasmid: pET28 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21-AI / References: UniProt: P0A8M3, threonine-tRNA ligase
#2: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical	ChemComp-1B2 / N-{[3-(2H-indazol-5-yl)phenyl]sulfonyl}-L-threoninamide Mass: 374.414 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₇H₁₈N₄O₄S
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 444 / 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: 3.31 Å³/Da / Density % sol: 62.84 %
Crystal grow	Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.9 Details: PEG 4000, MPD, sodium citrate, pH 5.9, vapor diffusion, hanging drop, temperature 298K

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Data collection

Diffraction source	Source: ROTATING ANODE / Type: RIGAKU RU300 / Wavelength: 1.54 Å
Detector	Type: MAR scanner 300 mm plate / Detector: IMAGE PLATE / Details: Mar345
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.54 Å / Relative weight: 1
Reflection	Resolution: 1.9→50 Å / Num. obs: 96015

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Phasing

Phasing

Method:

molecular replacement

Phasing MR

Model details: Phaser MODE: MR_AUTO

	Highest resolution	Lowest resolution
Rotation	2.5 Å	43.5 Å
Translation	2.5 Å	43.5 Å

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Processing

Software

Name	Version	Classification
SCALA		data scaling
PHASER	2.3.0	phasing
REFMAC	5.6.0117	refinement
PDB_EXTRACT	3.11	data extraction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.9→43.5 Å / Cor.coef. F_o:F_c: 0.908 / Cor.coef. F_o:F_c free: 0.879 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 7.936 / SU ML: 0.128 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.172 / ESU R Free: 0.163 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES: RESIDUAL ONLY

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.3033	4806	5 %	RANDOM
R_work	0.2655	-	-	-
obs	0.2674	96015	99.66 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

B_iso max: 76.35 Å² / B_iso mean: 32.6 Å² / B_iso min: 9.74 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.07 Å²	-0 Å²	0.01 Å²
2-	-	-0.05 Å²	-0 Å²
3-	-	-	-0 Å²

Refinement step

Cycle: LAST / Resolution: 1.9→43.5 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	6541	0	54	444	7039

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.014	0.019	6739
X-RAY DIFFRACTION	r_angle_refined_deg	1.576	1.959	9081
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.5	5	799
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	33.594	23.543	350
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	16.782	15	1222
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	17.289	15	62
X-RAY DIFFRACTION	r_chiral_restr	0.112	0.2	947
X-RAY DIFFRACTION	r_gen_planes_refined	0.008	0.021	5170

LS refinement shell

Resolution: 1.9→1.949 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.478	346	-
R_work	0.45	6639	-
all	-	6985	-
obs	-	-	99.99 %

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	0.0078	0.0529	0.0044	0.5561	0.1496	0.1089	-0.0149	-0.0023	-0.0093	-0.0137	0.0025	0.0003	-0.0013	0.0367	0.0124	0.0951	0.0065	-0.0083	0.0822	-0.0088	0.0688	39.5034	-39.9736	10.5695
2	0.4019	0.1406	0.2896	0.4471	-0.0711	0.285	0.0096	-0.0336	0.0132	0.022	-0.0219	0.0211	-0.0119	-0.014	0.0122	0.0668	0.0003	-0.0046	0.095	-0.0106	0.0631	29.5164	-29.6363	29.1209
3	0.1001	0.2421	-0.1237	1.7152	0.0453	0.3186	0.0533	0.0126	0.0017	-0.0177	-0.0914	-0.0241	0.005	-0.1151	0.0381	0.1156	-0.024	-0.0295	0.0965	-0.0164	0.0634	47.1729	-28.5683	36.0209
4	0.0292	0.0141	-0.0193	0.1739	-0.0764	0.0556	0.0076	-0.0097	-0.0275	0.0629	-0.0044	0.0328	0.0077	0.005	-0.0032	0.1024	-0.0037	0.0001	0.0857	-0.0143	0.065	26.1368	-33.9588	30.7624
5	0.3235	0.2853	0.2528	0.4288	0.0502	0.6854	0.0415	-0.0288	-0.0601	0.0466	-0.0374	-0.0246	0.0729	0.0147	-0.004	0.0787	-0.026	0.0102	0.0798	0.0087	0.0606	23.5095	-47.4691	40.0201
6	0.0564	0.1008	0.0072	0.3349	0.2538	0.7142	0.0008	-0.0357	-0.0158	0.0402	-0.0333	0.0485	0.0296	0.0399	0.0325	0.0964	-0.0055	0.0122	0.0925	0.0062	0.0723	24.5034	-40.137	34.0907
7	1.0107	-1.0621	-1.1794	1.6306	2.4289	4.3407	0.0667	-0.0832	-0.0354	0.058	0.048	0.0258	0.1269	-0.0403	-0.1147	0.0823	-0.0238	0.056	0.0878	0.0133	0.0861	21.1796	-31.3454	39.4422
8	0.2269	-0.0346	0.2465	0.3362	-0.241	0.5598	-0.0256	0.019	-0.0225	-0.0614	-0.0435	0.0015	-0.0218	-0.0263	0.0691	0.112	0.0211	-0.0179	0.0704	-0.0238	0.0621	27.3235	-35.887	-2.5351
9	0.4692	-0.8641	0.0351	1.6047	0.024	0.7095	0.0686	-0.0002	0.0101	-0.1578	-0.0272	-0.0212	0.0346	0.017	-0.0414	0.1137	0.0249	-0.0276	0.0772	-0.007	0.0542	30.0443	-42.1487	-9.2987
10	0.6939	-0.2074	0.1057	1.9659	-0.8901	0.7158	0.0939	0.1848	-0.1817	-0.2134	0.064	0.2304	0.1056	-0.0122	-0.1579	0.1334	0.0397	-0.063	0.1232	-0.0391	0.0747	19.587	-37.7804	-16.5454
11	7.2607	-6.537	4.9671	6.9914	-6.5607	7.4388	0.0337	0.1659	-0.5445	0.0432	0.0435	0.3772	-0.0851	-0.0439	-0.0772	0.1146	-0.0176	-0.0718	0.1274	-0.004	0.0977	18.1777	-45.6873	-10.0411
12	0.6347	0.3289	0.1465	1.1249	-1.3538	2.2156	0.0079	-0.0896	-0.0045	-0.1673	0.0337	0.053	0.2121	-0.1968	-0.0416	0.0903	0.0455	-0.0685	0.0959	-0.0391	0.0849	14.0349	-38.7576	-0.5155
13	0.5295	-0.0158	-0.2216	0.7311	-0.1529	0.1368	0.0278	-0.0653	0.0017	0.0446	-0.0391	0.0619	-0.036	0.0284	0.0112	0.0932	0.004	-0.0068	0.0776	-0.0091	0.0677	29.6564	-13.3276	29.3857
14	0.3161	-0.2348	0.3832	0.3682	0.6622	5.142	-0.0918	0.0745	-0.0447	0.0745	-0.0405	0.0831	-0.0152	0.179	0.1324	0.074	0.0072	-0.0321	0.0898	-0.0106	0.0746	28.6516	-19.0814	6.8987
15	1.0948	-0.1902	0.5054	0.1967	-0.2865	0.6673	0.022	-0.0528	-0.0026	-0.0052	-0.0771	-0.0327	0.041	0.0259	0.0551	0.0854	0.0116	-0.0117	0.0743	0.0099	0.0585	50.8752	-26.1009	15.7916
16	0.048	0.0506	-0.0954	0.3293	-0.111	0.1909	0.0047	0.0034	-0.009	-0.0201	-0.0239	-0.063	-0.0141	-0.0005	0.0193	0.0868	0.0143	-0.0041	0.0812	0.01	0.0681	47.9394	-28.0961	11.7392
17	0.013	-0.0507	0.0115	0.2741	-0.0008	0.145	-0.0097	0.0076	0.0203	0.0013	-0.0243	-0.0349	0.0012	0.0037	0.034	0.0882	0.0103	-0.0155	0.0915	0.0089	0.0645	43.8977	-15.3802	12.4872
18	0.2528	-0.0925	0.1801	0.3367	-0.1177	0.3334	-0.0234	0.0303	-0.0112	-0.016	-0.0352	-0.0112	-0.041	0.0475	0.0587	0.0892	-0.0067	-0.0142	0.0632	0.0266	0.0701	47.767	-6.1879	5.4799
19	0.2642	-0.2739	-0.2582	0.4217	0.1704	0.505	0.0362	0.0021	0.0425	-0.0538	-0.0401	-0.0609	-0.0607	0.0564	0.004	0.083	-0.0004	-0.0099	0.0766	0.0188	0.0606	46.9987	-13.6886	7.8967
20	0.8147	-0.4607	-0.4721	0.8025	1.0637	1.6238	-0.0805	0.0363	0.1303	0.0162	0.0845	-0.0829	0.0073	0.1576	-0.0039	0.069	0.0088	0.0134	0.0938	0.0329	0.0708	48.4909	-21.5609	0.6771
21	0.9012	0.2152	-0.0879	0.21	-0.1769	0.1833	0.0046	0.016	-0.0079	0.0192	-0.006	0.0442	-0.0183	-0.0088	0.0014	0.0743	0.0121	0.0037	0.0713	-0.0337	0.1028	13.9887	-13.5971	21.0429
22	1.5994	0.1876	-0.7733	0.8928	0.5348	0.8257	0.0218	-0.0107	-0.0025	0.0955	-0.0612	0.0661	0.0384	-0.0297	0.0393	0.0763	0.0192	0.0169	0.0672	-0.0115	0.0987	6.3602	-9.7356	28.7292
23	1.0957	-0.5989	-0.4027	0.5731	-0.0471	1.2121	-0.0285	0.1498	0.0298	-0.0259	0.0285	0.1088	-0.1353	-0.1267	0	0.0636	-0.0183	-0.0572	0.1303	0.0314	0.149	1.9806	-8.0581	16.7883
24	0.5433	-1.129	0.4319	4.606	-2.0495	0.9311	0.0574	0.2011	0.0342	0.0874	-0.05	0.0452	-0.0474	-0.0158	-0.0075	0.071	0.0296	-0.0184	0.1599	-0.0076	0.0703	14.7696	-9.9699	8.8818

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	241 - 274
2	X-RAY DIFFRACTION	2	A	275 - 312
3	X-RAY DIFFRACTION	3	A	313 - 326
4	X-RAY DIFFRACTION	4	A	327 - 413
5	X-RAY DIFFRACTION	5	A	414 - 466
6	X-RAY DIFFRACTION	6	A	467 - 501
7	X-RAY DIFFRACTION	7	A	502 - 516
8	X-RAY DIFFRACTION	8	A	517 - 576
9	X-RAY DIFFRACTION	9	A	577 - 596
10	X-RAY DIFFRACTION	10	A	597 - 611
11	X-RAY DIFFRACTION	11	A	612 - 619
12	X-RAY DIFFRACTION	12	A	620 - 643
13	X-RAY DIFFRACTION	13	B	242 - 274
14	X-RAY DIFFRACTION	14	B	275 - 289
15	X-RAY DIFFRACTION	15	B	290 - 313
16	X-RAY DIFFRACTION	16	B	314 - 359
17	X-RAY DIFFRACTION	17	B	360 - 400
18	X-RAY DIFFRACTION	18	B	401 - 467
19	X-RAY DIFFRACTION	19	B	468 - 501
20	X-RAY DIFFRACTION	20	B	502 - 516
21	X-RAY DIFFRACTION	21	B	517 - 568
22	X-RAY DIFFRACTION	22	B	569 - 600
23	X-RAY DIFFRACTION	23	B	601 - 627
24	X-RAY DIFFRACTION	24	B	628 - 639

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