PDB-8vtc: Crystal structure of Mycobacterium avium dihydrofolate reductase ...

ID or keywords:

Entry

Database: PDB / ID: 8vtc

Title

Crystal structure of Mycobacterium avium dihydrofolate reductase in complex with NADPH and trimethoprim

Components

Dihydrofolate reductase

Keywords

OXIDOREDUCTASE/INHIBITOR / dihydrofolate reductase / Mycobacterium avium / trimetoprim / OXIDOREDUCTASE / OXIDOREDUCTASE-INHIBITOR complex

Function / homology

Function and homology information

dihydrofolate metabolic process / dihydrofolate reductase / dihydrofolate reductase activity / folic acid metabolic process / tetrahydrofolate biosynthetic process / one-carbon metabolic process / NADP binding / cytosol
Similarity search - Function

Biological species

Mycobacterium avium (bacteria)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2 Å

Authors

Erlandsen, H. / Krucinska, J. / Wright, D.

Funding support

United States, 1items

Citation

Journal: To Be Published
Title: Long Residence Time Inhibitors of Dihydrofolate Reductase Display Potent Activity Against Mycobacterium Avium.
Authors: Wright, L. / Krucinska, J. / Erlandsen, H. / Haijan, B. / Cynamon, M. / Wright, D.

History

Deposition	Jan 26, 2024	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Mar 19, 2025	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	8vtc.cif.gz	171.9 KB	Display	PDBx/mmCIF format
PDB format	pdb8vtc.ent.gz	113.2 KB	Display	PDB format
PDBx/mmJSON format	8vtc.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8vtc_validation.pdf.gz	963.4 KB	Display	wwPDB validaton report
Full document	8vtc_full_validation.pdf.gz	963.4 KB	Display
Data in XML	8vtc_validation.xml.gz	10.2 KB	Display
Data in CIF	8vtc_validation.cif.gz	12.8 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/vt/8vtc ftp://data.pdbj.org/pub/pdb/validation_reports/vt/8vtc	HTTPS FTP

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Related structure data

Similar structure data	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 (10) #57 - Sep 2004 Catalase similarity (1)

Deposited unit

A: Dihydrofolate reductase

hetero molecules

19.5 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)	70.251, 70.251, 73.511
Angle α, β, γ (deg.)	90, 90, 90
Int Tables number	92
Space group name H-M	P4₁2₁2

#1: Protein	Dihydrofolate reductase Mass: 18451.822 Da / Num. of mol.: 1 / Fragment: residues 1-167 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mycobacterium avium (bacteria) / Gene: folA / Production host: Escherichia coli (E. coli) / References: UniProt: O30463, dihydrofolate reductase
#2: Chemical	ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE Mass: 745.421 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₁H₃₀N₇O₁₇P₃ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-TOP / TRIMETHOPRIM Mass: 290.318 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₄H₁₈N₄O₃ / Feature type: SUBJECT OF INVESTIGATION / Comment: antibiotic*YM
#4: Chemical	ChemComp-CL / CHLORIDE ION Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 46 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y
Has protein modification	N

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.46 Å³/Da / Density % sol: 49.95 % / Description: Rod-shaped
Crystal grow	Temperature: 277.15 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 55% MPD, 0.1 M Hepes pH 7.5 and 2 mM DTT

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Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

NSLS-II

/ Beamline: 17-ID-1 / Wavelength: 0.97933 Å

Detector

Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jun 20, 2019

Radiation

Monochromator: Double Crystal Monochromator, Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 0.97933 Å / Relative weight: 1

Reflection

Resolution: 2→29.564 Å / Num. obs: 12872 / % possible obs: 99.4 % / Redundancy: 1.8 % / CC_1/2: 0.999 / R_merge(I) obs: 0.024 / R_pim(I) all: 0.024 / R_rim(I) all: 0.034 / Net I/σ(I): 14

Reflection shell

Diffraction-ID: 1

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Mean I/σ(I) obs	Num. unique obs	CC_1/2	R_pim(I) all	R_rim(I) all	% possible all
8.94-29.55	1.5	0.014	30.1	183	0.999	0.014	0.019	97.6
2-2.05	1.9	0.206	2.9	891	0.921	0.206	0.292	96.9

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0425	refinement
REFMAC	5.8.0425	refinement
autoPROC		data reduction
XDS		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2→29.564 Å / Cor.coef. F_o:F_c: 0.97 / Cor.coef. F_o:F_c free: 0.934 / WR_factor R_free: 0.262 / WR_factor R_work: 0.174 / SU B: 9.377 / SU ML: 0.124 / Average fsc free: 0.9611 / Average fsc work: 0.9801 / Cross valid method: FREE R-VALUE / ESU R Free: 0.166
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2403	665	5.176 %
R_work	0.1666	12183	-
all	0.171	-	-
obs	-	12848	99.052 %

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: 41.22 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	1.722 Å²	-0 Å²	-0 Å²
2-	-	1.722 Å²	-0 Å²
3-	-	-	-3.444 Å²

Refinement step

Cycle: LAST / Resolution: 2→29.564 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1273	0	70	46	1389

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.007	0.012	1385
X-RAY DIFFRACTION	r_bond_other_d	0.002	0.016	1269
X-RAY DIFFRACTION	r_angle_refined_deg	1.71	1.82	1897
X-RAY DIFFRACTION	r_angle_other_deg	0.555	1.761	2901
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.699	5	165
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	18.641	5	26
X-RAY DIFFRACTION	r_dihedral_angle_other_2_deg	0.64	5	4
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.419	10	201
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	13.582	10	60
X-RAY DIFFRACTION	r_chiral_restr	0.066	0.2	203
X-RAY DIFFRACTION	r_gen_planes_refined	0.007	0.02	1699
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	340
X-RAY DIFFRACTION	r_nbd_refined	0.206	0.2	228
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.199	0.2	1184
X-RAY DIFFRACTION	r_nbtor_refined	0.18	0.2	670
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.083	0.2	727
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.144	0.2	59
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.087	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.406	0.2	6
X-RAY DIFFRACTION	r_nbd_other	0.311	0.2	31
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.174	0.2	5
X-RAY DIFFRACTION	r_mcbond_it	5.697	2.711	660
X-RAY DIFFRACTION	r_mcbond_other	5.701	465.063	660
X-RAY DIFFRACTION	r_mcangle_it	8.409	4.862	825
X-RAY DIFFRACTION	r_mcangle_other	8.406	10.057	826
X-RAY DIFFRACTION	r_scbond_it	6.949	2.968	725
X-RAY DIFFRACTION	r_scbond_other	6.95		726
X-RAY DIFFRACTION	r_scangle_it	9.924	5.328	1072
X-RAY DIFFRACTION	r_scangle_other	9.919	5.327	1073
X-RAY DIFFRACTION	r_lrange_it	15.178		5854
X-RAY DIFFRACTION	r_lrange_other	15.187		5843
X-RAY DIFFRACTION	r_rigid_bond_restr	4.45	3	1385

LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	R_factor all	Num. reflection all	Fsc free	Fsc work	% reflection obs (%)	WR_factor R_work
2-2.051	0.213	47	0.207	840	0.207	921	0.966	0.965	96.3084	0.19
2.051-2.107	0.297	38	0.182	863	0.187	912	0.936	0.974	98.7939	0.164
2.107-2.168	0.209	48	0.187	846	0.189	906	0.968	0.973	98.6755	0.166
2.168-2.235	0.283	35	0.182	793	0.187	837	0.948	0.977	98.9247	0.164
2.235-2.307	0.271	20	0.175	814	0.177	843	0.951	0.98	98.9324	0.161
2.307-2.388	0.324	31	0.169	769	0.174	806	0.929	0.981	99.2556	0.154
2.388-2.477	0.252	29	0.165	754	0.169	788	0.964	0.984	99.3655	0.15
2.477-2.578	0.229	38	0.169	712	0.172	754	0.973	0.984	99.4695	0.157
2.578-2.691	0.248	40	0.159	696	0.163	740	0.964	0.984	99.4595	0.148
2.691-2.822	0.301	54	0.166	644	0.177	702	0.948	0.983	99.4302	0.16
2.822-2.973	0.21	44	0.178	603	0.18	651	0.973	0.981	99.3856	0.169
2.973-3.151	0.253	56	0.173	573	0.18	632	0.958	0.982	99.5253	0.173
3.151-3.366	0.202	26	0.157	577	0.159	606	0.978	0.984	99.5049	0.161
3.366-3.632	0.231	25	0.169	537	0.172	563	0.961	0.982	99.8224	0.177
3.632-3.972	0.23	24	0.157	497	0.16	525	0.97	0.984	99.2381	0.173
3.972-4.431	0.162	43	0.137	435	0.14	478	0.982	0.989	100	0.163
4.431-5.098	0.228	20	0.135	405	0.138	426	0.973	0.989	99.7653	0.162
5.098-6.197	0.292	19	0.202	354	0.207	374	0.967	0.98	99.7326	0.237
6.197-8.578	0.326	23	0.191	276	0.201	299	0.951	0.98	100	0.233
8.578-29.564	0.194	5	0.17	195	0.17	200	0.971	0.979	100	0.212

Refinement TLS params.

Method: refined / Origin x: -15.2031 Å / Origin y: 19.1062 Å / Origin z: -2.7846 Å

	11	12	13	21	22	23	31	32	33
T	0.0163 Å²	-0.0116 Å²	0.0078 Å²	-	0.0396 Å²	-0.0199 Å²	-	-	0.0503 Å²
L	2.4048 °²	0.8055 °²	-0.0295 °²	-	2.8391 °²	-1.0765 °²	-	-	3.7114 °²
S	0.0213 Å °	-0.2349 Å °	0.0315 Å °	0.1116 Å °	-0.0235 Å °	0.0494 Å °	0.1045 Å °	-0.1184 Å °	0.0022 Å °

Refinement TLS group

Selection: ALL

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