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

ID or keywords:

Entry

Database: PDB / ID: 5scy

Title

Crystal Structure of Dihydrofolate Reductase from Mycobacterium tuberculosis bound to NADP and SDDC Inhibitor SDDC-1198

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 / 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 tuberculosis H37Rv (bacteria)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.4 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-1198
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	5scy.cif.gz	89.8 KB	Display	PDBx/mmCIF format
PDB format	pdb5scy.ent.gz	66 KB	Display	PDB format
PDBx/mmJSON format	5scy.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Summary document	5scy_validation.pdf.gz	1004.1 KB	Display	wwPDB validaton report
Full document	5scy_full_validation.pdf.gz	1004.2 KB	Display
Data in XML	5scy_validation.xml.gz	11.2 KB	Display
Data in CIF	5scy_validation.cif.gz	16.4 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/sc/5scy ftp://data.pdbj.org/pub/pdb/validation_reports/sc/5scy	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	5sd5-d 4x5h-d 6dpa-d 4phf-d 5a0g-2 5scn-d 6mbb-d 6dpe-d 5nff-6 6e3i-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

-
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

21.2 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)	29.580, 67.290, 72.250
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-HEI / 1-(2-{3-[(2,4-diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)piperidine-4-carboxylic acid Mass: 415.486 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₁H₂₉N₅O₄ / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₂H₆O₂
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 211 / 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: 1.9 Å³/Da / Density % sol: 35 % / Mosaicity: 0.162 °
Crystal grow	Temperature: 289 K / Method: vapor diffusion, sitting drop Details: JCSG+ E1 (284863e1): 1000 mM Sodium citrate dibasic trihydrate, 100mM Sodium cacodylate, 10mg/mL, cryo 20% EG, puck gtu5-7

-
Data collection

Diffraction

Mean temperature: 100 K

Diffraction source

Source:

SYNCHROTRON / Site:

APS

/ Beamline: 21-ID-G / Wavelength: 0.97856 Å

Detector

Type: RAYONIX MX-300 / Detector: CCD / Date: Feb 16, 2017

Radiation

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

Radiation wavelength

Wavelength: 0.97856 Å / Relative weight: 1

Reflection

Resolution: 1.4→50 Å / Num. obs: 28978 / % possible obs: 99 % / Observed criterion σ(I): -3 / B_iso Wilson estimate: 18.545 Å² / R_merge F obs: 0.999 / R_merge(I) obs: 0.05 / R_rim(I) all: 0.057 / Net I/σ(I): 17.74 / Num. measured all: 118547

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
1.4-1.44		0.793	0.531	2.32	7030	2097	1950	0.623	93
1.44-1.48		0.876	0.415	3.21	8040	2114	2048	0.48	96.9
1.48-1.52		0.913	0.34	4.12	8244	1975	1973	0.389	99.9
1.52-1.57		0.946	0.272	5.16	8239	1987	1984	0.312	99.8
1.57-1.62		0.965	0.218	6.39	7879	1880	1879	0.25	99.9
1.62-1.67		0.973	0.181	7.82	7729	1840	1840	0.207	100
1.67-1.74		0.982	0.151	9.14	7533	1804	1802	0.172	99.9
1.74-1.81		0.989	0.116	11.88	7152	1700	1696	0.133	99.8
1.81-1.89		0.993	0.09	15.06	6876	1649	1642	0.103	99.6
1.89-1.98		0.996	0.068	19.29	6627	1604	1600	0.078	99.8
1.98-2.09		0.997	0.057	22.63	6190	1489	1484	0.066	99.7
2.09-2.21		0.997	0.046	26.91	6007	1430	1427	0.053	99.8
2.21-2.37		0.998	0.044	28.22	5600	1357	1354	0.051	99.8
2.37-2.56		0.998	0.038	32.29	5235	1260	1256	0.043	99.7
2.56-2.8		0.999	0.033	36.02	4838	1174	1172	0.038	99.8
2.8-3.13		0.999	0.028	40.01	4400	1066	1062	0.032	99.6
3.13-3.61		0.999	0.024	45.06	3869	956	953	0.028	99.7
3.61-4.43		0.999	0.021	48.14	3252	818	817	0.024	99.9
4.43-6.26		0.999	0.019	47.59	2496	653	653	0.022	100
	6.26	0.999	0.021	44.42	1311	403	386	0.025	95.8

-
Processing

Software

Name	Version	Classification
XDS		data reduction
XSCALE		data scaling
PHENIX	dev_2196	refinement
PDB_EXTRACT	3.11	data extraction
PHENIX		model building
Coot		model building
PHENIX		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.4→33.645 Å / Occupancy max: 1 / Occupancy min: 0.25 / SU ML: 0.11 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 15.73 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.1706	2118	7.32 %
R_work	0.1482	26802	-
obs	0.1498	28920	99.05 %

Solvent computation

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

Displacement parameters

B_iso max: 55.19 Å² / B_iso mean: 16.1874 Å² / B_iso min: 6.22 Å²

Refinement step

Cycle: LAST / Resolution: 1.4→33.645 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1298	0	94	211	1603

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.006	1476
X-RAY DIFFRACTION	f_angle_d	0.918	2020
X-RAY DIFFRACTION	f_chiral_restr	0.076	212
X-RAY DIFFRACTION	f_plane_restr	0.005	276
X-RAY DIFFRACTION	f_dihedral_angle_d	23.672	575

LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 15

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Num. reflection all	% reflection obs (%)
1.4-1.4326	0.2352	149	0.2225	1602	1751	93
1.4326-1.4684	0.24	142	0.2031	1712	1854	96
1.4684-1.5081	0.2299	146	0.1885	1749	1895	100
1.5081-1.5525	0.1967	119	0.1826	1785	1904	100
1.5525-1.6026	0.2066	153	0.1788	1778	1931	100
1.6026-1.6599	0.1828	135	0.1632	1793	1928	100
1.6599-1.7263	0.1933	130	0.1633	1802	1932	100
1.7263-1.8049	0.1789	147	0.1529	1752	1899	100
1.8049-1.9001	0.1577	148	0.1454	1784	1932	100
1.9001-2.0191	0.1626	140	0.1404	1795	1935	100
2.0191-2.175	0.1522	138	0.1378	1806	1944	100
2.175-2.3938	0.1717	141	0.1478	1807	1948	100
2.3938-2.74	0.189	144	0.1434	1827	1971	100
2.74-3.4516	0.1386	149	0.1358	1843	1992	100
3.4516-33.6547	0.1562	137	0.1314	1967	2104	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	0.7302	0.0664	0.502	0.91	-0.0157	0.266	-0.0037	0.1459	0.1006	-0.0878	-0.0521	0.0256	-0.1851	0.1597	-0.0147	0.1023	0.0017	-0.0009	0.1	0.0176	0.0868	14.3806	13.6837	6.6319
2	1.7204	-0.2718	0.3557	1.6779	-0.5797	3.3462	0.0828	-0.0885	-0.1411	0.0577	-0.0319	0.029	0.1505	-0.0193	-0.0528	0.1171	-0.0124	-0.0095	0.0766	0.0068	0.0903	11.2065	-0.1958	23.4042
3	1.2755	-0.6709	-0.9704	2.1392	0.7733	1.6971	0.054	-0.0094	-0.0056	0.0153	-0.022	0.0406	-0.0251	-0.1073	-0.0319	0.048	-0.0081	-0.0155	0.0929	-0.004	0.0721	7.1337	3.4692	10.4094
4	1.5846	-0.5908	0.3509	2.3519	-0.1735	1.752	0.061	0.0867	-0.1184	-0.0558	-0.0393	0.0553	0.1243	-0.0466	-0.0226	0.0853	-0.0044	-0.0062	0.095	-0.0112	0.0878	10.3875	-5.3505	3.6995
5	0.0423	-0.3284	0.0118	2.3475	-0.2161	0.4838	0.0268	0.064	0.1833	-0.1921	-0.0408	-0.417	-0.1664	-0.0232	-0.0088	0.1366	0.0038	0.0197	0.122	-0.0024	0.1817	18.7464	2.837	-1.5787
6	0.9076	-0.1514	-0.1494	1.2921	0.2369	1.0848	0.0752	0.06	0.0375	-0.0429	-0.0392	-0.0758	-0.0438	0.0445	-0.0448	0.0735	-0.0041	-0.0023	0.0766	0.0055	0.0784	16.719	8.9313	11.2318
7	3.263	-2.0576	-1.78	2.0212	1.2459	1.713	-0.1411	-0.3358	-0.2025	0.3849	0.1337	-0.0831	0.33	0.2052	0.0839	0.2407	0.0407	-0.0383	0.1734	0.0221	0.1793	16.5942	0.006	28.9177
8	2.29	0.464	-1.3807	2.1823	-0.181	2.2273	0.0908	-0.1146	0.1678	0.08	0.0243	-0.2667	-0.1448	0.1422	-0.1168	0.1053	-0.0173	-0.0227	0.1343	-0.0207	0.1359	21.4081	14.2802	18.0376
9	5.8143	0.8537	-4.0802	0.539	-0.8869	3.5599	0.0458	-0.0442	0.0577	-0.0316	0.0538	-0.0251	0.03	0.0042	-0.1429	0.1123	-0.0222	-0.0084	0.0992	-0.0057	0.0865	8.1322	14.1518	23.2356

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details	Auth asym-ID
1	X-RAY DIFFRACTION	1	chain 'A' and (resid -8 through 9 )	A
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 10 through 24 )	A
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 25 through 49 )	A
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 50 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 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