[English] 日本語
Yorodumi
- PDB-4tzr: Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4tzr
TitleCalcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1561
ComponentsCalmodulin-domain protein kinase 1
KeywordsTRANSFERASE / serine/threonine protein kinase / calcium-binding / ATP-binding / bumped kinase inhibitor
Function / homology
Function and homology information


phosphorylation / protein serine/threonine kinase activity / calcium ion binding / ATP binding / membrane / cytoplasm
Similarity search - Function
EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / EF-hand domain pair / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 ...EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / EF-hand domain pair / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-UW2 / Calmodulin-domain protein kinase 1
Similarity search - Component
Biological speciesToxoplasma gondii (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2 Å
AuthorsMerritt, E.A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI089441 United States
Citation
Journal: J. Med. Chem. / Year: 2016
Title: Development of an Orally Available and Central Nervous System (CNS) Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related ...Title: Development of an Orally Available and Central Nervous System (CNS) Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis.
Authors: Vidadala, R.S. / Rivas, K.L. / Ojo, K.K. / Hulverson, M.A. / Zambriski, J.A. / Bruzual, I. / Schultz, T.L. / Huang, W. / Zhang, Z. / Scheele, S. / DeRocher, A.E. / Choi, R. / Barrett, L.K. / ...Authors: Vidadala, R.S. / Rivas, K.L. / Ojo, K.K. / Hulverson, M.A. / Zambriski, J.A. / Bruzual, I. / Schultz, T.L. / Huang, W. / Zhang, Z. / Scheele, S. / DeRocher, A.E. / Choi, R. / Barrett, L.K. / Siddaramaiah, L.K. / Hol, W.G. / Fan, E. / Merritt, E.A. / Parsons, M. / Freiberg, G. / Marsh, K. / Kempf, D.J. / Carruthers, V.B. / Isoherranen, N. / Doggett, J.S. / Van Voorhis, W.C. / Maly, D.J.
#1: Journal: Nat.Struct.Mol.Biol. / Year: 2010
Title: Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.
Authors: Ojo, K.K. / Larson, E.T. / Keyloun, K.R. / Castaneda, L.J. / Derocher, A.E. / Inampudi, K.K. / Kim, J.E. / Arakaki, T.L. / Murphy, R.C. / Zhang, L. / Napuli, A.J. / Maly, D.J. / Verlinde, C. ...Authors: Ojo, K.K. / Larson, E.T. / Keyloun, K.R. / Castaneda, L.J. / Derocher, A.E. / Inampudi, K.K. / Kim, J.E. / Arakaki, T.L. / Murphy, R.C. / Zhang, L. / Napuli, A.J. / Maly, D.J. / Verlinde, C.L. / Buckner, F.S. / Parsons, M. / Hol, W.G. / Merritt, E.A. / Van Voorhis, W.C.
#2: Journal: J.Med.Chem. / Year: 2012
Title: Multiple determinants for selective inhibition of apicomplexan calcium-dependent protein kinase CDPK1.
Authors: Larson, E.T. / Ojo, K.K. / Murphy, R.C. / Johnson, S.M. / Zhang, Z. / Kim, J.E. / Leibly, D.J. / Fox, A.M. / Reid, M.C. / Dale, E.J. / Perera, B.G. / Kim, J. / Hewitt, S.N. / Hol, W.G. / ...Authors: Larson, E.T. / Ojo, K.K. / Murphy, R.C. / Johnson, S.M. / Zhang, Z. / Kim, J.E. / Leibly, D.J. / Fox, A.M. / Reid, M.C. / Dale, E.J. / Perera, B.G. / Kim, J. / Hewitt, S.N. / Hol, W.G. / Verlinde, C.L. / Fan, E. / Van Voorhis, W.C. / Maly, D.J. / Merritt, E.A.
History
DepositionJul 10, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 27, 2014Provider: repository / Type: Initial release
Revision 1.1Sep 20, 2017Group: Author supporting evidence / Database references ...Author supporting evidence / Database references / Derived calculations / Other / Source and taxonomy / Structure summary
Category: citation / entity_src_gen ...citation / entity_src_gen / pdbx_audit_support / pdbx_database_status / pdbx_struct_assembly / pdbx_struct_assembly_prop / pdbx_struct_oper_list / struct_keywords
Item: _citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag ..._citation.journal_id_CSD / _entity_src_gen.pdbx_alt_source_flag / _pdbx_audit_support.funding_organization / _pdbx_database_status.pdb_format_compatible / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_assembly_prop.type / _pdbx_struct_assembly_prop.value / _pdbx_struct_oper_list.symmetry_operation / _struct_keywords.text
Revision 1.2Nov 8, 2017Group: Database references / Category: citation / citation_author
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
Revision 1.3Dec 11, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Dec 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength / refine_hist
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine_hist.number_atoms_total / _refine_hist.pdbx_number_atoms_nucleic_acid / _refine_hist.pdbx_number_atoms_protein

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Calmodulin-domain protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,6172
Polymers55,2271
Non-polymers3901
Water2,306128
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area22680 Å2
MethodPISA
Unit cell
Length a, b, c (Å)48.240, 73.090, 66.240
Angle α, β, γ (deg.)90.000, 100.380, 90.000
Int Tables number4
Space group name H-MP1211
Detailsbiological unit is the same as AU

-
Components

#1: Protein Calmodulin-domain protein kinase 1


Mass: 55226.914 Da / Num. of mol.: 1 / Fragment: UNP residues 30-507 / Mutation: N-term 29 residues replaced with His tag
Source method: isolated from a genetically manipulated source
Details: residues 1-29 were replaced with a cleavable His-tag plus linker during cloning; tag was cleaved prior to crystallization
Source: (gene. exp.) Toxoplasma gondii (eukaryote) / Gene: CDPK1 / Plasmid: AVA0421 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9BJF5
#2: Chemical ChemComp-UW2 / 1-{4-amino-3-[2-(cyclopropyloxy)quinolin-6-yl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}-2-methylpropan-2-ol


Mass: 390.438 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H22N6O2
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 128 / 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: 2.08 Å3/Da / Density % sol: 40.86 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 28% PEG 3350, 250 mM ammonium citrate, 2 mM EDTA, 5 mM DTT, 2 mM UW1561

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.97946 Å
DetectorType: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Jan 22, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2→48.64 Å / Num. obs: 30683 / % possible obs: 99.9 % / Redundancy: 7.4 % / CC1/2: 0.998 / Rmerge(I) obs: 0.152 / Rpim(I) all: 0.06 / Net I/σ(I): 9.6 / Num. measured all: 226046 / Scaling rejects: 53
Reflection shell

Diffraction-ID: 1 / Rejects: 0

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allCC1/2Rpim(I) all% possible all
2-2.057.22.2470.91622222480.1020.89699.1
8.94-48.6470.03143.625883700.9990.01399.4

-
Processing

Software
NameVersionClassification
Aimless0.1.26data scaling
REFMACrefinement
PDB_EXTRACT3.14data extraction
REFMAC5.8.0049refinement
RefinementResolution: 2→48.64 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.943 / WRfactor Rfree: 0.2175 / WRfactor Rwork: 0.1847 / FOM work R set: 0.7438 / SU B: 14.94 / SU ML: 0.188 / SU R Cruickshank DPI: 0.2268 / SU Rfree: 0.18 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.227 / ESU R Free: 0.18 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2416 1499 4.9 %RANDOM
Rwork0.2072 29165 --
obs0.2089 30664 99.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 141.41 Å2 / Biso mean: 50.165 Å2 / Biso min: 20.73 Å2
Baniso -1Baniso -2Baniso -3
1--0.08 Å2-0 Å2-0.23 Å2
2---0.37 Å2-0 Å2
3---0.5 Å2
Refinement stepCycle: final / Resolution: 2→48.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3691 0 34 128 3853
Biso mean--36.94 43.21 -
Num. residues----461
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0193860
X-RAY DIFFRACTIONr_bond_other_d0.0010.023720
X-RAY DIFFRACTIONr_angle_refined_deg1.5671.9685212
X-RAY DIFFRACTIONr_angle_other_deg0.80138597
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8295481
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.30224.783184
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.35915745
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.8491523
X-RAY DIFFRACTIONr_chiral_restr0.0920.2574
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.024456
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02859
X-RAY DIFFRACTIONr_mcbond_it3.2393.8171865
X-RAY DIFFRACTIONr_mcbond_other3.2273.8151863
X-RAY DIFFRACTIONr_mcangle_it5.0315.7072332
LS refinement shellResolution: 2→2.052 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.367 100 -
Rwork0.38 2143 -
all-2243 -
obs--99.12 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°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)
11.03570.54190.51381.06770.64791.9326-0.1765-0.02750.0443-0.40770.03190.1434-0.3756-0.15090.14460.16950.0021-0.06590.0879-0.0050.06772.8032-20.0707-41.0677
20.17090.1658-0.09660.53520.58631.3082-0.0224-0.0381-0.0342-0.0272-0.08770.03420.0333-0.06950.11010.0215-0.0002-0.03220.13120.00460.10655.0938-22.0797-25.5178
30.1727-0.02820.29040.6327-0.13840.5139-0.0057-0.06660.02170.065-0.0227-0.0249-0.0005-0.09050.02840.0144-0.0104-0.00960.18350.00670.05431.8934-11.7327-16.0511
43.99222.52910.72912.75610.71920.19230.14570.0459-0.25070.1073-0.13340.05880.0462-0.0249-0.01220.15330.0082-0.07980.0464-0.03240.0927-14.5528-9.2087-52.2374
53.51281.4708-1.85090.8241-0.63362.63750.0539-0.04890.177-0.02580.13610.0127-0.117-0.1136-0.190.0278-0.0214-0.01450.1495-0.04630.1035-16.59371.4232-21.9749
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A42 - 94
2X-RAY DIFFRACTION2A95 - 214
3X-RAY DIFFRACTION3A215 - 373
4X-RAY DIFFRACTION4A374 - 435
5X-RAY DIFFRACTION5A436 - 507

+
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