[English] 日本語
Yorodumi
- PDB-8f84: Crystal Structure of Dihydrofolate reductase (DHFR) from Mycobact... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8f84
TitleCrystal Structure of Dihydrofolate reductase (DHFR) from Mycobacterium ulcerans Agy99 in complex with NADP and inhibitor MAM787
ComponentsDihydrofolate reductase
KeywordsOXIDOREDUCTASE/INHIBITOR / SSGCID / STRUCTURAL GENOMICS / SEATTLE STRUCTURAL GENOMICS CENTER FOR INFECTIOUS DISEASE / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex / 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
Dihydrofolate reductase / Dihydrofolate reductase conserved site / Dihydrofolate reductase (DHFR) domain signature. / Dihydrofolate reductase (DHFR) domain profile. / Dihydrofolate reductase domain / Dihydrofolate reductase / Dihydrofolate reductase-like domain superfamily
Similarity search - Domain/homology
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Chem-XK8 / Dihydrofolate reductase
Similarity search - Component
Biological speciesMycobacterium ulcerans (bacteria)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.1 Å
AuthorsSeattle Structural Genomics Center for Infectious Disease / Seattle Structural Genomics Center for Infectious Disease (SSGCID)
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)75N93022C00036 United States
National Institutes of Health/Office of the DirectorS10OD030394 United States
CitationJournal: J.Med.Chem. / Year: 2024
Title: Rational Exploration of 2,4-Diaminopyrimidines as DHFR Inhibitors Active against Mycobacterium abscessus and Mycobacterium avium , Two Emerging Human Pathogens.
Authors: Andrade Meirelles, M. / Almeida, V.M. / Sullivan, J.R. / de Toledo, I. / Dos Reis, C.V. / Cunha, M.R. / Zigweid, R. / Shim, A. / Sankaran, B. / Woodward, E.L. / Seibold, S. / Liu, L. / Mian, ...Authors: Andrade Meirelles, M. / Almeida, V.M. / Sullivan, J.R. / de Toledo, I. / Dos Reis, C.V. / Cunha, M.R. / Zigweid, R. / Shim, A. / Sankaran, B. / Woodward, E.L. / Seibold, S. / Liu, L. / Mian, M.R. / Battaile, K.P. / Riley, J. / Duncan, C. / Simeons, F.R.C. / Ferguson, L. / Joji, H. / Read, K.D. / Lovell, S. / Staker, B.L. / Behr, M.A. / Pilli, R.A. / Counago, R.M.
History
DepositionNov 21, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 13, 2023Provider: repository / Type: Initial release
Revision 1.1Jun 19, 2024Group: Data collection / Category: diffrn / Item: _diffrn.ambient_temp
Revision 1.2Nov 6, 2024Group: Database references / Structure summary / Category: citation / citation_author / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _pdbx_entry_details.has_protein_modification
Revision 1.3Nov 27, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dihydrofolate reductase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,1833
Polymers19,0361
Non-polymers1,1482
Water3,513195
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)28.698, 66.374, 44.146
Angle α, β, γ (deg.)90.00, 91.44, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Dihydrofolate reductase


Mass: 19035.619 Da / Num. of mol.: 1 / Mutation: C89S/E96A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mycobacterium ulcerans (bacteria) / Strain: Agy99 / Gene: dfrA, MUL_2179 / Plasmid: MyulA.01062.a.B13 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: A0PQG8, 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-XK8 / 3-[2-(3-{[2,4-diamino-6-(4-hydroxybutyl)pyrimidin-5-yl]oxy}propoxy)phenyl]propanoic acid


Mass: 404.460 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H28N4O5 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 195 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.21 Å3/Da / Density % sol: 44.29 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: Morpheus F4: 12.5% PDB 1000, 12.5% PEG 3350, 12.5% MPD 0.02M of each monosaccharide (d-glucose, d-mannose, d-galactose, l-fucose, d-xylose, N-acetyld-glucosamine), 0.1M MES/imidazole pH 6.5 ...Details: Morpheus F4: 12.5% PDB 1000, 12.5% PEG 3350, 12.5% MPD 0.02M of each monosaccharide (d-glucose, d-mannose, d-galactose, l-fucose, d-xylose, N-acetyld-glucosamine), 0.1M MES/imidazole pH 6.5 , MyulA.01062.a.B13.PS38558 at 10 mg/mL. Tray: Tray 355D3/ MAM738 +NADP, Puck: CPS5110_06, Cryo: Direct

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 19-ID / Wavelength: 0.97949 Å
DetectorType: DECTRIS EIGER2 XE 9M / Detector: PIXEL / Date: Oct 30, 2022
RadiationMonochromator: Double Crystal Si 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97949 Å / Relative weight: 1
ReflectionResolution: 1.1→44.13 Å / Num. obs: 65812 / % possible obs: 98.3 % / Redundancy: 6.6 % / CC1/2: 1 / Rmerge(I) obs: 0.024 / Rpim(I) all: 0.01 / Rrim(I) all: 0.026 / Χ2: 0.96 / Net I/σ(I): 30.2 / Num. measured all: 433825
Reflection shellResolution: 1.1→1.12 Å / % possible obs: 76.2 % / Redundancy: 4.3 % / Rmerge(I) obs: 0.236 / Num. measured all: 10791 / Num. unique obs: 2486 / CC1/2: 0.954 / Rpim(I) all: 0.125 / Rrim(I) all: 0.269 / Χ2: 1 / Net I/σ(I) obs: 5.2

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.1→23.78 Å / SU ML: 0.06 / Cross valid method: FREE R-VALUE / σ(F): 1.21 / Phase error: 12.22 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.144 3297 5.01 %
Rwork0.1254 --
obs0.1263 65775 98.25 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.1→23.78 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1246 0 77 195 1518
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0071458
X-RAY DIFFRACTIONf_angle_d1.0532017
X-RAY DIFFRACTIONf_dihedral_angle_d12.311598
X-RAY DIFFRACTIONf_chiral_restr0.069222
X-RAY DIFFRACTIONf_plane_restr0.013253
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.1-1.120.16181090.13871954X-RAY DIFFRACTION75
1.12-1.130.13851230.12782293X-RAY DIFFRACTION86
1.13-1.150.11471170.1112602X-RAY DIFFRACTION98
1.15-1.170.1381600.10922592X-RAY DIFFRACTION100
1.17-1.190.1421310.10432670X-RAY DIFFRACTION100
1.19-1.210.11841470.11112614X-RAY DIFFRACTION100
1.21-1.230.13831610.1182625X-RAY DIFFRACTION100
1.23-1.260.13071350.11582641X-RAY DIFFRACTION100
1.26-1.290.1241310.10762646X-RAY DIFFRACTION100
1.29-1.320.12361300.10752651X-RAY DIFFRACTION100
1.32-1.350.11461320.10672663X-RAY DIFFRACTION100
1.35-1.390.14431110.10862674X-RAY DIFFRACTION100
1.39-1.430.12711150.10822660X-RAY DIFFRACTION100
1.43-1.470.14371270.11242677X-RAY DIFFRACTION100
1.47-1.530.12391320.11272658X-RAY DIFFRACTION100
1.53-1.590.13381480.11182625X-RAY DIFFRACTION100
1.59-1.660.12191440.11572630X-RAY DIFFRACTION100
1.66-1.750.15551450.12212652X-RAY DIFFRACTION100
1.75-1.860.13711490.12942646X-RAY DIFFRACTION100
1.86-20.13231440.12562652X-RAY DIFFRACTION100
2-2.20.14471550.12712657X-RAY DIFFRACTION100
2.2-2.520.15121300.13142637X-RAY DIFFRACTION100
2.52-3.170.13441600.13792677X-RAY DIFFRACTION100
3.17-23.780.16991610.13552682X-RAY DIFFRACTION100

+
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