[English] 日本語
Yorodumi
- PDB-6rxc: Leishmania major pteridine reductase 1 (LmPTR1) in complex with i... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6rxc
TitleLeishmania major pteridine reductase 1 (LmPTR1) in complex with inhibitor 4 (NMT-C0026)
Components(Pteridine reductase 1) x 2
KeywordsOXIDOREDUCTASE / Leishmania major / pteridine reductase / LmPTR1 / pteridine based inhibitors
Function / homology
Function and homology information


pteridine reductase / 6,7-dihydropteridine reductase activity / pteridine reductase activity / tetrahydrobiopterin biosynthetic process / response to methotrexate / oxidoreductase activity / cytosol
Similarity search - Function
Pteridine reductase / Short-chain dehydrogenase/reductase, conserved site / Short-chain dehydrogenases/reductases family signature. / Enoyl-(Acyl carrier protein) reductase / Short-chain dehydrogenase/reductase SDR / NAD(P)-binding Rossmann-like Domain / NAD(P)-binding domain superfamily / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-KMK / Chem-NDP / Pteridine reductase 1
Similarity search - Component
Biological speciesLeishmania major (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsDi Pisa, F. / Dello Iacono, L. / Pozzi, C. / Mangani, S.
Funding support1items
OrganizationGrant numberCountry
European Union603240
CitationJournal: J.Med.Chem. / Year: 2022
Title: Multitarget, Selective Compound Design Yields Potent Inhibitors of a Kinetoplastid Pteridine Reductase 1.
Authors: Pohner, I. / Quotadamo, A. / Panecka-Hofman, J. / Luciani, R. / Santucci, M. / Linciano, P. / Landi, G. / Di Pisa, F. / Dello Iacono, L. / Pozzi, C. / Mangani, S. / Gul, S. / Witt, G. / ...Authors: Pohner, I. / Quotadamo, A. / Panecka-Hofman, J. / Luciani, R. / Santucci, M. / Linciano, P. / Landi, G. / Di Pisa, F. / Dello Iacono, L. / Pozzi, C. / Mangani, S. / Gul, S. / Witt, G. / Ellinger, B. / Kuzikov, M. / Santarem, N. / Cordeiro-da-Silva, A. / Costi, M.P. / Venturelli, A. / Wade, R.C.
History
DepositionJun 7, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 15, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 13, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author / database_2
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Jan 24, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Pteridine reductase 1
B: Pteridine reductase 1
C: Pteridine reductase 1
D: Pteridine reductase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)127,88312
Polymers122,9234
Non-polymers4,9608
Water11,728651
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area20390 Å2
ΔGint-128 kcal/mol
Surface area35420 Å2
MethodPISA
Unit cell
Length a, b, c (Å)95.267, 103.445, 136.749
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Pteridine reductase 1 / H region methotrexate resistance protein


Mass: 30722.850 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Leishmania major (eukaryote) / Gene: PTR1, HMTXR, L1063.01, LmjF23.0270, LmjF_23_0270 / Plasmid: pET15b / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q01782, pteridine reductase
#2: Protein Pteridine reductase 1 / H region methotrexate resistance protein


Mass: 30738.850 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Leishmania major (eukaryote) / Gene: PTR1, HMTXR, L1063.01, LmjF23.0270, LmjF_23_0270 / Plasmid: pET15b / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q01782, pteridine reductase
#3: Chemical
ChemComp-NDP / NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE


Mass: 745.421 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H30N7O17P3
#4: Chemical
ChemComp-KMK / methyl 1-[4-[[2,4-bis(azanyl)pteridin-6-yl]methyl-(3-oxidanylpropyl)amino]phenyl]carbonylpiperidine-4-carboxylate


Mass: 494.546 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H30N8O4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 651 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.74 Å3/Da / Density % sol: 55.12 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.3
Details: Protein solution: 12.5 mg/mL in 20 mM Sodium Acetate pH 5.3 and 10 mM DTT; Crystallization buffer: 12% PEG4600, 100 mM Sodium Acetate pH 5.5 and 120-160 mM Calcium Acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 4, 2015
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.1→82.5 Å / Num. obs: 78229 / % possible obs: 98.7 % / Observed criterion σ(I): 2 / Redundancy: 4.5 % / Biso Wilson estimate: 24.1 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.11 / Rpim(I) all: 0.057 / Rrim(I) all: 0.124 / Net I/σ(I): 8.2
Reflection shellResolution: 2.1→2.21 Å / Redundancy: 4.5 % / Rmerge(I) obs: 0.383 / Mean I/σ(I) obs: 3.6 / Num. unique obs: 11390 / CC1/2: 0.836 / Rpim(I) all: 0.2 / Rrim(I) all: 0.434 / % possible all: 99.4

-
Processing

Software
NameVersionClassification
REFMAC5.8.0238refinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5L4N

5l4n


Resolution: 2.1→82.5 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.898 / SU B: 5.273 / SU ML: 0.142 / Cross valid method: THROUGHOUT / ESU R: 0.215 / ESU R Free: 0.192
RfactorNum. reflection% reflectionSelection details
Rfree0.26082 3890 5 %RANDOM
Rwork0.21345 ---
obs0.21586 74289 98.39 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 28.602 Å2
Baniso -1Baniso -2Baniso -3
1--0.01 Å20 Å20 Å2
2--0.01 Å20 Å2
3----0.01 Å2
Refine analyzeLuzzati coordinate error obs: 0.265 Å
Refinement stepCycle: 1 / Resolution: 2.1→82.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7687 0 336 651 8674
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0128212
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.9231.66611238
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.64951031
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.64319.971339
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.062151163
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.8451559
X-RAY DIFFRACTIONr_chiral_restr0.1260.21132
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.026186
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it3.0472.6694154
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it4.1813.9745166
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.6772.9564058
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined7.02337.81613207
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.1→2.155 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.317 290 -
Rwork0.246 5481 -
obs--98.99 %

+
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