PDB-7f3z: Double mutant Plasmodium falciparum dihydrofolate reductase-thymi...

ID or keywords:

Entry

Database: PDB / ID: 7f3z

Title

Double mutant Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS-K1, C59R+S108N) complexed with Trimethoprim (TOP), NADPH and dUMP

Components

Bifunctional dihydrofolate reductase-thymidylate synthase

Keywords

STRUCTURAL PROTEIN / PfDHFR /

Trimethoprim /

dihydrofolate reductase /

Plasmodium falciparum

Function / homology

Function and homology information

thymidylate synthase activity / dTMP biosynthetic process /

dihydrofolate reductase activity / tetrahydrofolate biosynthetic process / one-carbon metabolic process /

Biological species

Plasmodium falciparum (malaria parasite P. falciparum)

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT / Resolution: 2.6 Å

Authors

Vanichtanankul, J. / Tanramluk, D. / Chitnumsub, P. / Yuvaniyama, J. / Yuthavong, Y.

Citation

Journal: Structure / Year: 2022
Title: MANORAA: A machine learning platform to guide protein-ligand design by anchors and influential distances.
Authors: Tanramluk, D. / Pakotiprapha, D. / Phoochaijaroen, S. / Chantravisut, P. / Thampradid, S. / Vanichtanankul, J. / Narupiyakul, L. / Akavipat, R. / Yuvaniyama, J.

History

Deposition	Jun 17, 2021	Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0	Sep 22, 2021	Provider: repository / Type: Initial release
Revision 1.1	Mar 16, 2022	Group: Database references / Category: citation / citation_author Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _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 / _citation_author.identifier_ORCID
Revision 1.2	Nov 29, 2023	Group: Data collection / Derived calculations / Refinement description Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	7f3z.cif.gz	250.9 KB	Display	PDBx/mmCIF format
PDB format	pdb7f3z.ent.gz	192.5 KB	Display	PDB format
PDBx/mmJSON format	7f3z.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/f3/7f3z ftp://data.pdbj.org/pub/pdb/validation_reports/f3/7f3z	HTTPS FTP

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Related structure data

Related structure data	7f3yC 3qgtS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	3jsu-d 3um8-d 3dga-d 3qgt-d 3dg8-d 1j3j-d 6a2o-d 4dpd-d 7f3y-d 3um6-d 3um5-d 6a2k-d 6lhi-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	#34 - Oct 2002 Dihydrofolate Reductase similarity (8) #57 - Sep 2004 Catalase similarity (1)

Deposited unit

A: Bifunctional dihydrofolate reductase-thymidylate synthase

B: Bifunctional dihydrofolate reductase-thymidylate synthase

hetero molecules

147 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)	56.332, 153.739, 164.119
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁

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Protein , 1 types, 2 molecules AB

#1: Protein	Bifunctional dihydrofolate reductase-thymidylate synthase Mass: 71909.078 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum) Gene: dhfr-ts / Production host: Escherichia coli (E. coli) / References: UniProt: C3S7P8

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Non-polymers , 5 types, 202 molecules

#2: Chemical	ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate Mass: 745.421 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₃₀N₇O₁₇P₃ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-UMP / 2'-DEOXYURIDINE 5'-MONOPHOSPHATE / DUMP / Deoxyuridine monophosphate Mass: 308.182 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₉H₁₃N₂O₈P / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-TOP / TRIMETHOPRIM / Trimethoprim Mass: 290.318 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C₁₄H₁₈N₄O₃ / Feature type: SUBJECT OF INVESTIGATION / Comment: antibiotic*YM
#5: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol Mass: 92.094 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C₃H₈O₃ / Feature type: SUBJECT OF INVESTIGATION
#6: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 194 / 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: 2.47 Å³/Da / Density % sol: 55.2 %
Crystal grow	Temperature: 297 K / Method: microbatch / Details: 28.5% PEG4000, 0.8 M CH3COONH4 0.08 M CH3COONa

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: ROTATING ANODE / Type: RIGAKU R-AXIS IV / Wavelength: 1.5418 Å
Detector	Type: RIGAKU RAXIS / Detector: IMAGE PLATE / Date: Jun 13, 2003
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.5418 Å / Relative weight: 1
Reflection	Resolution: 2.6→51.54 Å / Num. obs: 43724 / % possible obs: 97 % / Redundancy: 4.17 % / CC_1/2: 0.994 / R_sym value: 0.083 / Net I/σ(I): 10.1
Reflection shell	Resolution: 2.6→2.69 Å / Num. unique obs: 3746 / CC_1/2: 0.523

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0267	refinement
CrystalClear		data reduction
CrystalClear		data scaling
MOLREP		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 3QGT

3qgt

Resolution: 2.6→39.782 Å / Cor.coef. F_o:F_c: 0.952 / Cor.coef. F_o:F_c free: 0.918 / SU B: 13.308 / SU ML: 0.269 / Cross valid method: FREE R-VALUE / ESU R: 0.869 / ESU R Free: 0.323
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2531	2178	4.989 %
R_work	0.1979	41482	-
all	0.201	-	-
obs	-	43660	97.373 %

Solvent computation

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

Displacement parameters

B_iso mean: 57.552 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.322 Å²	-0 Å²	-0 Å²
2-	-	-0.724 Å²	0 Å²
3-	-	-	0.402 Å²

Refinement step

Cycle: LAST / Resolution: 2.6→39.782 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	9110	0	190	194	9494

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.008	0.013	9520
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.017	8932
X-RAY DIFFRACTION	r_angle_refined_deg	1.602	1.646	12872
X-RAY DIFFRACTION	r_angle_other_deg	1.166	1.586	20560
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	8.213	5	1090
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	38.228	23.808	520
X-RAY DIFFRACTION	r_dihedral_angle_other_2_deg	4.694	10	2
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	19.775	15	1712
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	18.773	15	38
X-RAY DIFFRACTION	r_chiral_restr	0.067	0.2	1216
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.02	10672
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	2294
X-RAY DIFFRACTION	r_nbd_refined	0.21	0.2	1896
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.189	0.2	8762
X-RAY DIFFRACTION	r_nbtor_refined	0.176	0.2	4366
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.079	0.2	4580
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.18	0.2	276
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.096	0.2	3
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.248	0.2	38
X-RAY DIFFRACTION	r_nbd_other	0.24	0.2	89
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.114	0.2	10
X-RAY DIFFRACTION	r_mcbond_it	3.772	5.916	4378
X-RAY DIFFRACTION	r_mcbond_other	3.768	5.915	4377
X-RAY DIFFRACTION	r_mcangle_it	5.714	8.867	5462
X-RAY DIFFRACTION	r_mcangle_other	5.713	8.868	5463
X-RAY DIFFRACTION	r_scbond_it	3.869	6.246	5142
X-RAY DIFFRACTION	r_scbond_other	3.869	6.246	5143
X-RAY DIFFRACTION	r_scangle_it	5.915	9.218	7410
X-RAY DIFFRACTION	r_scangle_other	5.915	9.218	7411
X-RAY DIFFRACTION	r_lrange_it	8.255	65.8	10470
X-RAY DIFFRACTION	r_lrange_other	8.242	65.799	10457

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 (%)
2.6-2.667	0.313	128	0.284	2385	X-RAY DIFFRACTION	76.9914
2.667-2.74	0.354	138	0.285	2832	X-RAY DIFFRACTION	94.0469
2.74-2.82	0.319	162	0.261	2927	X-RAY DIFFRACTION	98.5013
2.82-2.907	0.291	141	0.238	2824	X-RAY DIFFRACTION	100
2.907-3.002	0.285	147	0.239	2764	X-RAY DIFFRACTION	98.8791
3.002-3.107	0.344	154	0.233	2677	X-RAY DIFFRACTION	100
3.107-3.224	0.303	136	0.221	2562	X-RAY DIFFRACTION	99.1547
3.224-3.356	0.299	118	0.222	2520	X-RAY DIFFRACTION	99.4721
3.356-3.505	0.253	108	0.209	2409	X-RAY DIFFRACTION	100
3.505-3.676	0.312	132	0.218	2270	X-RAY DIFFRACTION	99.5854
3.676-3.874	0.259	108	0.204	2207	X-RAY DIFFRACTION	99.7415
3.874-4.109	0.222	116	0.195	2072	X-RAY DIFFRACTION	99.772
4.109-4.393	0.215	105	0.169	1958	X-RAY DIFFRACTION	99.8065
4.393-4.744	0.163	112	0.142	1826	X-RAY DIFFRACTION	99.8969
4.744-5.196	0.209	76	0.15	1704	X-RAY DIFFRACTION	100
5.196-5.807	0.281	88	0.194	1541	X-RAY DIFFRACTION	99.8774
5.807-6.703	0.249	73	0.21	1373	X-RAY DIFFRACTION	99.793
6.703-8.202	0.276	61	0.184	1189	X-RAY DIFFRACTION	99.4431
8.202-11.57	0.175	47	0.119	928	X-RAY DIFFRACTION	98.8844
11.57-39.782	0.251	28	0.222	514	X-RAY DIFFRACTION	90.7873

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