[English] 日本語
Yorodumi
- PDB-6vsd: Mycobacterium tuberculosis dihydrofolate reductase in complex wit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vsd
TitleMycobacterium tuberculosis dihydrofolate reductase in complex with 3-((thiophen-2-ylthio)methyl)benzoic acid (fragment 13)
ComponentsDihydrofolate reductase
KeywordsBIOSYNTHETIC PROTEIN / folate pathway
Function / homology
Function and homology information


dihydrofolate metabolic process / NADP+ binding / folic acid metabolic process / glycine biosynthetic process / dihydrofolate reductase / dihydrofolate reductase activity / tetrahydrofolate biosynthetic process / one-carbon metabolic process / NADP binding / cytosol
Similarity search - Function
Dihydrofolate Reductase, subunit A / Dihydrofolate Reductase, subunit A / Dihydrofolate reductase / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase domain / Dihydrofolate reductase / Dihydrofolate reductase (DHFR) domain profile. / Dihydrofolate reductase-like domain superfamily / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
: / 3-(thiophen-2-ylsulfanylmethyl)benzoic acid / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / PHOSPHATE ION / Dihydrofolate reductase
Similarity search - Component
Biological speciesMycobacterium tuberculosis (bacteria)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.693 Å
AuthorsRibeiro, J.A. / Dias, M.V.B.
Funding support Brazil, 1items
OrganizationGrant numberCountry
Sao Paulo Research Foundation (FAPESP)2018/00351-1 Brazil
CitationJournal: Acs Infect Dis. / Year: 2020
Title: Using a Fragment-Based Approach to Identify Alternative Chemical Scaffolds Targeting Dihydrofolate Reductase fromMycobacterium tuberculosis.
Authors: Ribeiro, J.A. / Hammer, A. / Libreros-Zuniga, G.A. / Chavez-Pacheco, S.M. / Tyrakis, P. / de Oliveira, G.S. / Kirkman, T. / El Bakali, J. / Rocco, S.A. / Sforca, M.L. / Parise-Filho, R. / ...Authors: Ribeiro, J.A. / Hammer, A. / Libreros-Zuniga, G.A. / Chavez-Pacheco, S.M. / Tyrakis, P. / de Oliveira, G.S. / Kirkman, T. / El Bakali, J. / Rocco, S.A. / Sforca, M.L. / Parise-Filho, R. / Coyne, A.G. / Blundell, T.L. / Abell, C. / Dias, M.V.B.
History
DepositionFeb 11, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 15, 2020Provider: repository / Type: Initial release
Revision 1.1Aug 26, 2020Group: Database references / Derived calculations
Category: citation / citation_author ...citation / citation_author / pdbx_struct_conn_angle / struct_conn
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id
Revision 1.2Oct 11, 2023Group: 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 visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dihydrofolate reductase
B: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,08310
Polymers35,7872
Non-polymers2,2968
Water5,585310
1
A: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,0425
Polymers17,8931
Non-polymers1,1494
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,0415
Polymers17,8931
Non-polymers1,1484
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4760 Å2
ΔGint-46 kcal/mol
Surface area15250 Å2
MethodPISA
Unit cell
Length a, b, c (Å)61.745, 71.171, 71.798
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Dihydrofolate reductase /


Mass: 17893.293 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria)
Strain: ATCC 25618 / H37Rv / Gene: folA, dfrA, Rv2763c, MTV002.28c / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P9WNX1, dihydrofolate reductase

-
Non-polymers , 6 types, 318 molecules

#2: Chemical ChemComp-JBB / 3-(thiophen-2-ylsulfanylmethyl)benzoic acid


Mass: 250.337 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C12H10O2S2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-NAP / NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / 2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE / Nicotinamide adenine dinucleotide phosphate


Mass: 743.405 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H28N7O17P3
#4: Chemical ChemComp-CO / COBALT (II) ION


Mass: 58.933 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Co
#5: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#6: Chemical ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 310 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.2 Å3/Da / Density % sol: 44.2 %
Crystal growTemperature: 297 K / Method: vapor diffusion, hanging drop
Details: 1.6 M ammonium sulfate, 100 mM MES (2-(N-morpholino) ethanesulfonic acid), pH 6.5, 10 mM CoCl2

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: LNLS / Beamline: W01B-MX2 / Wavelength: 1.48 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Mar 23, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.48 Å / Relative weight: 1
Reflection twinOperator: -h,l,k / Fraction: 0.32
ReflectionResolution: 1.69→46.81 Å / Num. obs: 35767 / % possible obs: 99.4 % / Redundancy: 11.4 % / CC1/2: 0.999 / Rmerge(I) obs: 0.073 / Rpim(I) all: 0.022 / Rrim(I) all: 0.076 / Net I/σ(I): 21 / Num. measured all: 409192
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.69-1.727.40.9571214016500.690.3661.0281.888.3
8.96-46.8110.40.04730432940.9990.0150.0545.199.6

-
Processing

Software
NameVersionClassification
Aimless0.5.27data scaling
PHENIX1.14refinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1df7

1df7


Resolution: 1.693→46.639 Å / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 27.45
RfactorNum. reflection% reflection
Rfree0.2096 1844 5.16 %
Rwork0.1709 --
obs0.1745 35710 99.34 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 82.98 Å2 / Biso mean: 27.0975 Å2 / Biso min: 12.68 Å2
Refinement stepCycle: final / Resolution: 1.693→46.639 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2484 0 140 310 2934
Biso mean--27.79 37.08 -
Num. residues----318
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0072692
X-RAY DIFFRACTIONf_angle_d1.0153679
X-RAY DIFFRACTIONf_chiral_restr0.054386
X-RAY DIFFRACTIONf_plane_restr0.006467
X-RAY DIFFRACTIONf_dihedral_angle_d19.0461519
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 13

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.6957-1.74150.3811350.3842501263692
1.7415-1.79270.35771420.2982550269295
1.7927-1.85050.27561440.26722581272595
1.8505-1.91660.28921470.24692537268495
1.9166-1.99320.25441450.24062590273595
1.9932-2.08380.2751510.23592557270894
2.0838-2.19350.22711460.21522597274395
2.1935-2.33070.24681170.20572593271096
2.3307-2.51020.24251120.19232626273896
2.5102-2.76190.23431150.17832654276996
2.7619-3.15970.19751680.15582600276894
3.1597-3.97360.1861480.12282662281095
3.9736-17.85630.14841620.11532754291694
Refinement TLS params.Method: refined / Origin x: 22.8678 Å / Origin y: 0.331 Å / Origin z: 17.779 Å
111213212223313233
T0.1545 Å2-0.0014 Å2-0.0196 Å2-0.1439 Å2-0.0182 Å2--0.1845 Å2
L0.7446 °2-0.326 °2-0.135 °2-0.3038 °2-0.0923 °2--0.1422 °2
S0.0024 Å °-0.0024 Å °0.0338 Å °-0.011 Å °-0.0177 Å °-0.0451 Å °-0.0061 Å °0.013 Å °0.0146 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA1 - 159
2X-RAY DIFFRACTION1allB1 - 159
3X-RAY DIFFRACTION1allC2
4X-RAY DIFFRACTION1allC3
5X-RAY DIFFRACTION1allD1 - 2
6X-RAY DIFFRACTION1allE1 - 2
7X-RAY DIFFRACTION1allS1 - 303
8X-RAY DIFFRACTION1allS304 - 326
9X-RAY DIFFRACTION1allS327 - 334
10X-RAY DIFFRACTION1allF2
11X-RAY DIFFRACTION1allG1

+
About Yorodumi

-
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

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

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

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
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

Read more