[English] 日本語
Yorodumi- PDB-8ta1: Crystal Structure of Dihydrofolate reductase (DHFR) from Mycobact... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ta1 | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal Structure of Dihydrofolate reductase (DHFR) from Mycobacterium ulcerans Agy99 in complex with NADP and inhibitor MAM907 | ||||||
Components | Dihydrofolate reductase | ||||||
Keywords | OXIDOREDUCTASE/INHIBITOR / SSGCID / STRUCTURAL GENOMICS / SEATTLE STRUCTURAL GENOMICS CENTER FOR INFECTIOUS DISEASE / Dihydrofolate reductase / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex / OXIDOREDUCTASE / OXIDOREDUCTASE-INHIBITOR complex | ||||||
Function / homology | Function and homology information dihydrofolate reductase / dihydrofolate reductase activity / tetrahydrofolate biosynthetic process / one-carbon metabolic process / NADP binding Similarity search - Function | ||||||
Biological species | Mycobacterium ulcerans (bacteria) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.5 Å | ||||||
Authors | Seattle Structural Genomics Center for Infectious Disease / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8ta1.cif.gz | 90.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8ta1.ent.gz | 64.4 KB | Display | PDB format |
PDBx/mmJSON format | 8ta1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ta1_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8ta1_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 8ta1_validation.xml.gz | 11.3 KB | Display | |
Data in CIF | 8ta1_validation.cif.gz | 16.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ta/8ta1 ftp://data.pdbj.org/pub/pdb/validation_reports/ta/8ta1 | HTTPS FTP |
-Related structure data
Related structure data | 7k6cC 8f80C 8f81C 8f82C 8f83C 8f84C 8f85C 8ta0C 8tbrC C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 19035.619 Da / Num. of mol.: 1 / Fragment: MyulA.01062.a.B13 / 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) / Strain (production host): BL21(DE3) / References: UniProt: A0PQG8, dihydrofolate reductase |
---|
-Non-polymers , 6 types, 218 molecules
#2: Chemical | ChemComp-NA / | ||
---|---|---|---|
#3: Chemical | ChemComp-ACT / | ||
#4: Chemical | ChemComp-EII / Mass: 414.498 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H30N4O4 / Feature type: SUBJECT OF INVESTIGATION | ||
#5: Chemical | ChemComp-NAP / | ||
#6: Chemical | #7: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
---|---|
Has protein modification | N |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.2 Å3/Da / Density % sol: 44.22 % |
---|---|
Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 4.6 Details: Berkeley H8: 30% (w/v) PEG 4000, 100 mM Sodium acetate / Hydrochloric acid pH 4.6, 200 mM Ammonium acetate. Plate 13388 H8 drop 1. MyulA.01062.a.B13.PS38720 at 8.9 mg/mL. 2mM MAM907 and 2mM ...Details: Berkeley H8: 30% (w/v) PEG 4000, 100 mM Sodium acetate / Hydrochloric acid pH 4.6, 200 mM Ammonium acetate. Plate 13388 H8 drop 1. MyulA.01062.a.B13.PS38720 at 8.9 mg/mL. 2mM MAM907 and 2mM NADP added to the protein prior to crystallization. Plate 13388 well H8 drop 1, Cryo: 80% crystallant + 20% PEG 200 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SEALED TUBE / Type: BRUKER D8 QUEST / Wavelength: 1.5418 Å |
Detector | Type: Bruker PHOTON III / Detector: PIXEL / Date: Jun 21, 2023 |
Radiation | Monochromator: HELIOS MULTILAYER / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 1.5→44.11 Å / Num. obs: 26509 / % possible obs: 100 % / Redundancy: 8.7 % / CC1/2: 0.998 / Rmerge(I) obs: 0.102 / Rpim(I) all: 0.037 / Rrim(I) all: 0.109 / Χ2: 0.98 / Net I/σ(I): 18.1 / Num. measured all: 230896 |
Reflection shell | Resolution: 1.5→1.53 Å / % possible obs: 100 % / Redundancy: 5.8 % / Rmerge(I) obs: 1.247 / Num. measured all: 7525 / Num. unique obs: 1304 / CC1/2: 0.476 / Rpim(I) all: 0.571 / Rrim(I) all: 1.378 / Χ2: 0.78 / Net I/σ(I) obs: 1.5 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.5→22.27 Å / SU ML: 0.14 / Cross valid method: FREE R-VALUE / σ(F): 1.03 / Phase error: 17.37 / Stereochemistry target values: ML
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.5→22.27 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|