PDB-4zyu: Human GAR transformylase in complex with GAR and N-{4-[4-(2-Amino...

ID or keywords:

Entry

Database: PDB / ID: 4zyu

Title

Human GAR transformylase in complex with GAR and N-{4-[4-(2-Amino-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-6-yl)-butyl]benzoyl}-L-glutamic acid (AGF50)

Components

Trifunctional purine biosynthetic protein adenosine-3

Keywords

TRANSFERASE/TRANSFERASE INHIBITOR / gar transformylase / antifolate / TRANSFERASE-TRANSFERASE INHIBITOR complex

Function / homology

Function and homology information

phosphoribosylformylglycinamidine cyclo-ligase / phosphoribosylformylglycinamidine cyclo-ligase activity / adenine biosynthetic process / phosphoribosylamine-glycine ligase / phosphoribosylamine-glycine ligase activity / phosphoribosylglycinamide formyltransferase 1 / purine ribonucleoside monophosphate biosynthetic process / phosphoribosylglycinamide formyltransferase activity / 'de novo' XMP biosynthetic process / brainstem development ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 1.95 Å

Authors

Deis, S.M. / Dann III, C.E.

Funding support

United States, 2items

Organization	Grant number	Country
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	GM094472	United States
National Institutes of Health/National Cancer Institute (NIH/NCI)	CA166711	United States

Citation

Journal: Biochemistry / Year: 2016
Title: Structural and Enzymatic Analysis of Tumor-Targeted Antifolates That Inhibit Glycinamide Ribonucleotide Formyltransferase.
Authors: Deis, S.M. / Doshi, A. / Hou, Z. / Matherly, L.H. / Gangjee, A. / Dann, C.E.

History

Deposition	May 22, 2015	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Apr 20, 2016	Provider: repository / Type: Initial release
Revision 1.1	Feb 22, 2017	Group: Database references
Revision 1.2	Sep 20, 2017	Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3	Dec 4, 2019	Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4	Sep 27, 2023	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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PDBx/mmCIF format	4zyu.cif.gz	101.8 KB	Display	PDBx/mmCIF format
PDB format	pdb4zyu.ent.gz	75.9 KB	Display	PDB format
PDBx/mmJSON format	4zyu.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	4zyu_validation.pdf.gz	1.1 MB	Display	wwPDB validaton report
Full document	4zyu_full_validation.pdf.gz	1.1 MB	Display
Data in XML	4zyu_validation.xml.gz	11.3 KB	Display
Data in CIF	4zyu_validation.cif.gz	15.6 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/zy/4zyu ftp://data.pdbj.org/pub/pdb/validation_reports/zy/4zyu	HTTPS FTP

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Related structure data

Related structure data	4zytC 4zyvC 4zywC 4zyxC 4zyyC 4zyzC 4zz0C 4x74 PDB Unreleased entryS 1mej 1meo 1njs 1rbm 1rbq 1rby 1rbz 1rc0 1rc1 1zlx 1zly 4ew2 4ew3 4zz1 4zz2 4zz3 C: citing same article (ref.) S: Starting model for refinement
Similar structure data	4zz1-d 4zyw-d 4zz3-d 6eoa-d 4zyy-d 4zyz-d 4zz2-d 4zyv-d 6e87-d 4zz0-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	#104 - Aug 2008 Selenocysteine Synthase similarity (6) #215 - Nov 2017 Aspartate Transcarbamoylase similarity (4) #192 - Dec 2015 Vancomycin similarity (4) #154 - Oct 2012 Citric Acid Cycle similarity (3) #187 - Jul 2015 New Delhi Metallo-β-Lactamase similarity (4) #137 - May 2011 Cytochrome bc1 similarity (1)

Deposited unit

A: Trifunctional purine biosynthetic protein adenosine-3

hetero molecules

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

1

Idetical with deposited unit
defined by author

Unit cell

Length a, b, c (Å)	75.202, 75.202, 100.971
Angle α, β, γ (deg.)	90.000, 90.000, 120.000
Int Tables number	154
Space group name H-M	P3₂21

#1: Protein	Trifunctional purine biosynthetic protein adenosine-3 Mass: 22810.139 Da / Num. of mol.: 1 / Fragment: gar transformylase domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GART, PGFT, PRGS / Plasmid: pET22B / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta(DE3)pLysS References: UniProt: P22102, phosphoribosylglycinamide formyltransferase 1
#2: Chemical	ChemComp-GAR / GLYCINAMIDE RIBONUCLEOTIDE Mass: 284.160 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₇H₁₃N₂O₈P
#3: Chemical	ChemComp-3YA / N-{4-[4-(2-amino-4-oxo-1,4-dihydrothieno[2,3-d]pyrimidin-6-yl)butyl]benzoyl}-L-glutamic acid Mass: 472.514 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₂H₂₄N₄O₆S
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 124 / 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: 3.88 Å³/Da / Density % sol: 68.32 %
Crystal grow	Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 18 % PEG4000, 2 % PEG400, 0.33 M NaCl

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Data collection

Diffraction

Mean temperature: 100 K

Diffraction source

Source:

SYNCHROTRON / Site:

ALS

/ Beamline: 4.2.2 / Wavelength: 1.0001 Å

Detector

Type: RDI CMOS_8M / Detector: CMOS / Date: Aug 24, 2014

Radiation

Monochromator: Rosenbaum-Rock Si(111) sagitally focused monochromator
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 1.0001 Å / Relative weight: 1

Reflection

Resolution: 1.95→50 Å / Num. obs: 24596 / % possible obs: 99.5 % / Redundancy: 10.5 % / B_iso Wilson estimate: 19.29 Å² / R_merge(I) obs: 0.075 / R_pim(I) all: 0.024 / R_rim(I) all: 0.079 / Χ²: 0.967 / Net I/av σ(I): 27.682 / Net I/σ(I): 21 / Num. measured all: 257914

Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique all	CC_1/2	R_pim(I) all	R_rim(I) all	Χ²	% possible all
1.95-1.98	7	0.374	1200	0.934	0.149	0.405	0.697	97.3
1.98-2.02	8.1	0.361	1204	0.948	0.137	0.387	0.947	99.7
2.02-2.06	9.2	0.306	1202	0.974	0.107	0.325	0.897	100
2.06-2.1	10.1	0.255	1242	0.988	0.085	0.269	0.845	100
2.1-2.15	10.7	0.231	1215	0.992	0.074	0.242	0.874	100
2.15-2.2	11	0.203	1208	0.992	0.064	0.213	0.922	100
2.2-2.25	11	0.181	1209	0.994	0.057	0.189	0.99	100
2.25-2.31	11.1	0.168	1216	0.993	0.053	0.176	1.116	100
2.31-2.38	11.2	0.133	1236	0.995	0.042	0.139	0.841	100
2.38-2.46	11.1	0.112	1215	0.996	0.035	0.118	0.751	100
2.46-2.54	11.1	0.104	1232	0.997	0.033	0.109	0.817	100
2.54-2.65	11.2	0.093	1214	0.997	0.029	0.098	0.883	100
2.65-2.77	11.1	0.088	1241	0.998	0.027	0.092	0.92	100
2.77-2.91	11.1	0.081	1236	0.996	0.026	0.085	1.017	100
2.91-3.1	11.1	0.079	1227	0.997	0.025	0.082	1.11	100
3.1-3.33	11.1	0.077	1255	0.996	0.024	0.08	1.24	100
3.33-3.67	11	0.074	1247	0.997	0.023	0.078	1.294	100
3.67-4.2	11	0.065	1267	0.997	0.02	0.068	1.098	99.9
4.2-5.29	10.7	0.06	1260	0.997	0.019	0.064	0.99	99.9
5.29-50	9.7	0.058	1270	0.997	0.019	0.061	0.931	93.1

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Phasing

Phasing	Method: molecular replacement

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Processing

Software

Name	Version	Classification
SCALEPACK		data scaling
PHASER	2.5.6	phasing
PHENIX	phenix.refine 1.9	refinement
PDB_EXTRACT	3.15	data extraction
Coot		model building

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4X74

4x74
PDB Unreleased entry

Resolution: 1.95→39.901 Å / SU ML: 0.16 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 18.76 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.2071	1983	8.29 %
R_work	0.1789	21943	-
obs	0.1812	23926	96.86 %

Solvent computation

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

Displacement parameters

B_iso max: 102.63 Å² / B_iso mean: 33.3889 Å² / B_iso min: 7.98 Å²

Refinement step

Cycle: final / Resolution: 1.95→39.901 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1491	0	51	124	1666
B_iso mean	-	-	49.86	29.67	-
Num. residues	-	-	-	-	200

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.008	1647
X-RAY DIFFRACTION	f_angle_d	1.078	2253
X-RAY DIFFRACTION	f_chiral_restr	0.045	265
X-RAY DIFFRACTION	f_plane_restr	0.005	294
X-RAY DIFFRACTION	f_dihedral_angle_d	12.656	595

LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 14

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Num. reflection all	% reflection obs (%)
1.9483-1.9971	0.2389	99	0.2249	1077	1176	68
1.9971-2.051	0.2514	134	0.2245	1490	1624	93
2.051-2.1114	0.212	143	0.1973	1591	1734	100
2.1114-2.1795	0.2119	145	0.1838	1583	1728	100
2.1795-2.2574	0.1941	142	0.1785	1618	1760	100
2.2574-2.3478	0.2044	147	0.1742	1605	1752	100
2.3478-2.4547	0.2153	143	0.1916	1579	1722	100
2.4547-2.584	0.2126	144	0.1911	1621	1765	100
2.584-2.7459	0.2088	146	0.199	1607	1753	100
2.7459-2.9579	0.2279	147	0.1949	1595	1742	100
2.9579-3.2554	0.1991	144	0.1888	1654	1798	100
3.2554-3.7262	0.2189	146	0.171	1627	1773	100
3.7262-4.6934	0.1747	156	0.1507	1644	1800	100
4.6934-39.9092	0.2096	147	0.1591	1652	1799	95

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	2.0334	-1.1544	1.4147	1.6426	-2.7494	5.7194	-0.019	0.4224	0.0231	-0.6761	0.1693	0.4221	0.6576	-0.232	-0.2356	0.4024	-0.1564	-0.1073	0.2629	0.1265	0.2669	34.4147	-25.5499	-26.3368
2	5.1346	1.146	4.1707	0.5951	1.0414	3.4789	0.1204	0.142	-0.3756	-0.1924	-0.0126	-0.1435	0.3925	0.2404	-0.1222	0.2868	-0.0043	0.0048	0.1206	0.0535	0.1742	44.9996	-22.3912	-24.0306
3	5.4265	1.2658	1.1061	0.9133	1.7579	3.8658	-0.1092	0.5879	-0.8066	-0.91	0.0836	0.3026	0.5214	-0.2387	-0.088	0.7465	-0.0961	-0.1545	0.2062	-0.0032	0.4305	36.2766	-31.0423	-30.043
4	1.2417	0.0694	-0.9225	0.0406	0.14	1.6699	-0.5389	0.6169	0.4816	-0.9081	0.2164	0.9736	-0.0395	-0.5907	0.2857	0.8338	-0.2104	-0.3968	0.4458	0.0169	0.9272	25.2505	-33.2472	-28.393
5	3.7163	1.2222	0.1017	2.5079	-0.5623	1.745	-0.1797	0.2353	0.0666	-0.1945	0.1632	0.3141	0.0295	-0.1974	-0.1547	0.4369	-0.3029	-0.1187	0.609	0.2658	0.6837	21.5317	-28.8393	-22.0625
6	1.7456	0.6784	-1.1778	0.5898	-0.8419	1.6891	-0.0667	0.2528	0.0938	-0.1984	0.3489	0.4767	0.1877	-0.6972	-0.3586	0.2631	-0.164	-0.0789	0.4619	0.2266	0.3656	26.4939	-22.5545	-22.3364
7	0.5943	0.6393	-0.9771	2.4804	-0.5321	1.7836	-0.048	-0.1099	-0.2005	0.0067	0.0703	0.3399	0.1511	-0.4476	-0.0506	0.0957	-0.0437	0.0005	0.246	0.0621	0.177	30.0122	-9.1127	-32.7296
8	5.894	-0.2642	-2.1923	2.1775	2.274	3.6718	0.0329	0.3361	0.3085	0.1566	-0.101	0.632	0.1194	-0.5354	0.0556	0.2058	-0.0105	0.0749	0.5446	0.2032	0.3978	22.8218	-10.6618	-24.6867
9	1.4597	-0.9263	0.0733	1.1479	-0.2839	6.2744	-0.0501	0.1371	-0.033	-0.0656	0.0471	0.0809	-0.2598	0.184	-0.0082	0.1202	-0.0445	-0.0022	0.1465	0.0292	0.0726	38.3322	-4.7143	-39.0134
10	0.4766	-0.3705	0.1658	1.016	-1.7277	8.5854	0.0115	-0.0224	-0.2636	0.0712	0.0249	0.1033	0.2509	-0.0151	-0.01	0.1083	-0.0395	-0.0043	0.1187	0.0313	0.1371	40.0995	-13.4842	-32.375
11	7.8134	-2.5282	-2.5587	7.1538	2.4683	6.972	-0.4685	-0.8237	0.4108	1.035	0.3446	0.7207	-0.9152	-0.9118	0.0765	0.4349	0.1082	0.0583	0.3747	0.024	0.2552	34.1655	-8.1394	-13.026

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details	Auth asym-ID
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 808 through 818 )	A
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 819 through 835 )	A
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 836 through 856 )	A
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 857 through 870 )	A
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 871 through 884 )	A
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 885 through 906 )	A
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 907 through 945 )	A
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 946 through 954 )	A
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 955 through 968 )	A
10	X-RAY DIFFRACTION	10	chain 'A' and (resid 969 through 992 )	A
11	X-RAY DIFFRACTION	11	chain 'A' and (resid 993 through 1007 )	A

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