PDB-5sd3: Crystal Structure of Dihydrofolate Reductase from Mycobacterium t...

ID or keywords:

Entry

Database: PDB / ID: 5sd3

Title

Crystal Structure of Dihydrofolate Reductase from Mycobacterium tuberculosis bound to NADP and SDDC Inhibitor SDDC-1088

Components

Dihydrofolate reductase

Keywords

OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / Mycobacterium tuberculosis / DHFR / NADP / Folate / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID

Function / homology

Function and homology information

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

Biological species

Mycobacterium tuberculosis H37Rv (bacteria)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.3 Å

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID)

Funding support

United States, 1items

Citation

Journal: to be published
Title: Crystal Structure of Dihydrofolate Reductase from Mycobacterium tuberculosis bound to NADP and SDDC Inhibitor SDDC-1088
Authors: Mayclin, S.J. / Fairman, J.W. / Dranow, D.M. / Conrady, D.G. / Fox III, D. / Lukacs, C.M. / Lorimer, D.D. / Horanyi, P.S. / Edwards, T.E. / Abendroth, J.

History

Deposition	Dec 20, 2021	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Feb 9, 2022	Provider: repository / Type: Initial release
Revision 1.1	Mar 2, 2022	Group: Other / Structure summary Category: pdbx_SG_project / pdbx_database_status / struct_keywords Item: _pdbx_database_status.SG_entry / _struct_keywords.text
Revision 1.2	May 22, 2024	Group: Data collection / Category: chem_comp_atom / chem_comp_bond

Structure viewer	Molecule: MolmilJmol/JSmol

-
Download

PDBx/mmCIF format	5sd3.cif.gz	90.9 KB	Display	PDBx/mmCIF format
PDB format	pdb5sd3.ent.gz	67.2 KB	Display	PDB format
PDBx/mmJSON format	5sd3.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Summary document	5sd3_validation.pdf.gz	1006.5 KB	Display	wwPDB validaton report
Full document	5sd3_full_validation.pdf.gz	1006.7 KB	Display
Data in XML	5sd3_validation.xml.gz	11.1 KB	Display
Data in CIF	5sd3_validation.cif.gz	16.4 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/sd/5sd3 ftp://data.pdbj.org/pub/pdb/validation_reports/sd/5sd3	HTTPS FTP

-
Group deposition

ID	G_1002223 (26 entries) 5scm 5scn 5sco 5scp 5scq 5scr 5scs 5sct 5scu 5scv
Title	DHFR structures, SSGCID
Type	ground state
Description	human and M. tuberculosis DHFR structures bound to ligands

-
Related structure data

Similar structure data	5scu-d 5sd5-d 5sco-d 5sd4-d 5scz-d 5scn-d 7k62-1 5scs-d 2ki3-d 5scv-2 Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

-
Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#34 - Oct 2002 Dihydrofolate Reductase similarity (8)

Deposited unit

A: Dihydrofolate reductase

hetero molecules

21.3 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)	29.560, 67.430, 72.040
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁

Details

biological unit is a monomer, the same as asu

#1: Protein	Dihydrofolate reductase Mass: 19832.365 Da / Num. of mol.: 1 / Fragment: MtDHFR Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mycobacterium tuberculosis H37Rv (bacteria) Strain: ATCC 25618 / H37Rv / Gene: folA, dfrA, Rv2763c, MTV002.28c / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P9WNX1, dihydrofolate reductase
#2: Chemical	ChemComp-NAP / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE Mass: 743.405 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₁H₂₈N₇O₁₇P₃
#3: Chemical	ChemComp-H9I / 3-{2-[(3-{[(2,4-diamino-6-ethylpyrimidin-5-yl)oxy]methyl}oxetan-3-yl)methoxy]phenyl}propanoic acid Mass: 402.444 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₀H₂₆N₄O₅ / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C₂H₆O₂
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 212 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

-
Experiment

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

-
Sample preparation

Crystal	Density Matthews: 1.8 Å³/Da / Density % sol: 32 % / Mosaicity: 0.111 °
Crystal grow	Temperature: 289 K / Method: vapor diffusion, sitting drop Details: PACT C7 (292926c7): 200mM Sodium chloride, 100mM HEPES pH7, 20% PEG6000, 10mg/mL, cryo 20% EG, puck kpw8-8

-
Data collection

Diffraction

Mean temperature: 100 K

Diffraction source

Source:

SYNCHROTRON / Site:

APS

/ Beamline: 21-ID-G / Wavelength: 0.97857 Å

Detector

Type: RAYONIX MX-300 / Detector: CCD / Date: Jul 20, 2017

Radiation

Monochromator: C 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 0.97857 Å / Relative weight: 1

Reflection

Resolution: 1.3→50 Å / Num. obs: 35541 / % possible obs: 98 % / Observed criterion σ(I): -3 / B_iso Wilson estimate: 17.162 Å² / R_merge F obs: 0.998 / R_merge(I) obs: 0.062 / R_rim(I) all: 0.067 / Net I/σ(I): 17.03 / Num. measured all: 236777

Reflection shell

Resolution (Å)	Highest resolution (Å)	R_merge F obs	R_merge(I) obs	Mean I/σ(I) obs	Num. measured obs	Num. possible	Num. unique obs	R_rim(I) all	% possible all
1.3-1.33		0.854	0.394	3.07	8874	2634	2172	0.448	82.5
1.33-1.37		0.916	0.343	3.9	11030	2568	2353	0.385	91.6
1.37-1.41		0.945	0.299	5.11	14549	2535	2520	0.329	99.4
1.41-1.45		0.967	0.251	6.72	15910	2389	2389	0.273	100
1.45-1.5		0.979	0.207	8.63	17126	2391	2390	0.223	100
1.5-1.55		0.984	0.17	10.45	16536	2289	2289	0.183	100
1.55-1.61		0.99	0.143	12.25	15855	2200	2200	0.155	100
1.61-1.68		0.993	0.12	14.45	15345	2126	2126	0.129	100
1.68-1.75		0.993	0.106	16.39	14950	2065	2064	0.114	100
1.75-1.84		0.996	0.085	19.5	14240	1964	1963	0.091	99.9
1.84-1.94		0.996	0.074	22.52	13429	1864	1862	0.08	99.9
1.94-2.06		0.997	0.064	25.7	12820	1779	1777	0.069	99.9
2.06-2.2		0.997	0.059	27.66	11944	1664	1662	0.064	99.9
2.2-2.37		0.997	0.057	28.74	11196	1559	1559	0.062	100
2.37-2.6		0.997	0.053	30.99	10318	1463	1459	0.057	99.7
2.6-2.91		0.997	0.051	32.5	9276	1312	1310	0.056	99.8
2.91-3.36		0.998	0.047	34.11	8223	1177	1171	0.05	99.5
3.36-4.11		0.997	0.045	35.58	6954	1013	1009	0.049	99.6
4.11-5.81		0.997	0.044	35.58	5377	798	796	0.047	99.7
	5.81	0.998	0.043	33.46	2825	477	470	0.047	98.5

-
Processing

Software

Name	Version	Classification
XDS		data reduction
XSCALE		data scaling
PHENIX	dev_2829	refinement
PDB_EXTRACT	3.11	data extraction
PHENIX		model building
Coot		model building
PHENIX		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.3→27.073 Å / Occupancy max: 1 / Occupancy min: 0.25 / SU ML: 0.12 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 16.53 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.1631	2026	5.7 %
R_work	0.1509	33514	-
obs	0.1517	35540	97.99 %

Solvent computation

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

Displacement parameters

B_iso max: 63.91 Å² / B_iso mean: 15.5222 Å² / B_iso min: 5.93 Å²

Refinement step

Cycle: LAST / Resolution: 1.3→27.073 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1290	0	97	212	1599

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.006	1476
X-RAY DIFFRACTION	f_angle_d	0.95	2020
X-RAY DIFFRACTION	f_chiral_restr	0.08	212
X-RAY DIFFRACTION	f_plane_restr	0.007	275
X-RAY DIFFRACTION	f_dihedral_angle_d	23.806	572

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 (%)
1.3-1.3325	0.2847	106	0.2231	1970	2076	82
1.3325-1.3685	0.238	143	0.202	2189	2332	91
1.3685-1.4088	0.2111	161	0.1896	2400	2561	99
1.4088-1.4543	0.2115	153	0.1735	2361	2514	100
1.4543-1.5062	0.1691	133	0.167	2417	2550	100
1.5062-1.5665	0.1736	135	0.1627	2457	2592	100
1.5665-1.6378	0.2002	161	0.1592	2409	2570	100
1.6378-1.7242	0.167	146	0.154	2414	2560	100
1.7242-1.8322	0.1731	151	0.154	2413	2564	100
1.8322-1.9736	0.1611	137	0.1461	2469	2606	100
1.9736-2.1721	0.1582	143	0.1453	2430	2573	100
2.1721-2.4862	0.1521	151	0.1503	2475	2626	100
2.4862-3.1317	0.1504	137	0.1472	2496	2633	100
3.1317-27.0787	0.139	169	0.1316	2614	2783	100

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	0.9282	-0.035	0.5243	1.093	-0.6588	2.698	0.0665	0.0118	-0.0371	0.0237	-0.0634	0.0149	0.0268	0.087	-0.0051	0.0674	0.0075	-0.0098	0.046	-0.005	0.0692	12.8944	6.8189	14.4744
2	1.9905	-1.2342	-1.3271	2.6391	1.1449	1.7941	0.0595	-0.006	-0.0435	0.0266	-0.0214	0.0427	-0.023	-0.0908	-0.0519	0.0494	-0.0092	-0.022	0.0811	-0.0024	0.0608	7.2442	3.5394	10.5749
3	1.6164	-1.5639	2.4896	4.2588	-2.1559	4.7284	0.0943	-0.0996	-0.2001	-0.0094	0.059	0.3857	0.1239	-0.3229	-0.1834	0.0613	-0.001	-0.0001	0.1186	-0.0071	0.1181	3.1171	-3.6755	6.9495
4	7.5237	-2.8624	0.9469	4.6648	-0.0376	2.5761	0.0757	0.1647	-0.0764	-0.0748	-0.0446	-0.2011	0.2096	0.0586	-0.018	0.0931	0.0071	0.0127	0.0805	-0.0027	0.0367	14.9518	-6.6683	1.5444
5	2.1408	-2.1625	0.7837	3.1184	-1.9892	1.8362	-0.0747	0.1409	0.2884	-0.0371	-0.0857	-0.535	-0.1699	0.1099	0.1373	0.1358	-0.0028	0.0024	0.1227	-0.0064	0.1716	18.4433	2.8886	-1.3939
6	1.604	0.0977	-0.5689	1.6526	-0.5587	2.3677	0.088	0.0406	0.0363	-0.0538	-0.027	-0.0373	-0.0606	0.041	-0.0674	0.0563	-0.0025	-0.0107	0.0413	-0.0014	0.054	16.7251	8.8685	11.0348
7	6.8184	-7.1266	-6.0783	7.4581	6.3483	5.4379	-0.2325	-0.485	-0.2069	0.678	0.3034	-0.1583	0.4759	0.3251	0.0082	0.22	0.027	-0.0535	0.1427	0.0243	0.1792	16.4879	-0.0021	28.8592
8	5.8604	1.9474	-3.0721	3.1357	0.6394	3.2949	0.1802	-0.0048	0.3223	-0.0693	0.0482	-0.4473	-0.254	0.0406	-0.1937	0.0815	-0.0155	-0.0304	0.1092	-0.0175	0.073	20.952	14.7246	17.7314
9	9.2508	6.2186	0.0694	4.2102	0.136	0.3266	-0.0932	0.0376	0.108	-0.2206	0.179	0.2554	0.0967	-0.148	-0.0479	0.1218	-0.0245	0.0013	0.1125	0.0006	0.0768	2.5505	12.2909	27.8347
10	4.6375	0.6638	-5.6256	0.1224	-0.7971	6.8015	0.1819	0.0241	0.2645	-0.0191	0.023	-0.0444	-0.1227	0.0543	-0.2605	0.1105	-0.0138	0.0142	0.082	0.0007	0.1089	14.2326	16.8356	17.8018

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details	Auth asym-ID
1	X-RAY DIFFRACTION	1	chain 'A' and (resid -6 through 24 )	A
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 25 through 49 )	A
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 50 through 60 )	A
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 61 through 76 )	A
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 77 through 89 )	A
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 90 through 115 )	A
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 116 through 125 )	A
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 126 through 139 )	A
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 140 through 150 )	A
10	X-RAY DIFFRACTION	10	chain 'A' and (resid 151 through 159 )	A

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

Version 3 of the EMDB header file is now the official format.
The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

Thousand views of thousand structures

Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Group deposition

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

-Movie

-Structure viewers

+Viewer log

-This page

-This web site

-Options

+Open data

-Basic information

-Structure visualization

-Downloads & links

-Download

-Validation report

-Group deposition

-Related structure data

-Links

-Assembly

-Components

-Experimental details

-Experiment

-Sample preparation

-Data collection

-Processing

+About Yorodumi

-News

-Feb 9, 2022. New format data for meta-information of EMDB entries

-Aug 12, 2020. Covid-19 info

+Mar 5, 2020. Novel coronavirus structure data

+Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+Jul 12, 2017. Major update of PDB

-Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Group deposition

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi