[English] 日本語
Yorodumi
- PDB-4c0c: Crystal structure of Trypanosoma cruzi CYP51 bound to the inhibit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4c0c
TitleCrystal structure of Trypanosoma cruzi CYP51 bound to the inhibitor (R)-N-(3-(1H-indol-3-yl)-1-oxo-1-(pyridin-4-ylamino)propan-2-yl)-4-(4-(2,4-difluorophenyl)piperazin-1-yl)-2-fluorobenzamide.
ComponentsSTEROL 14-ALPHA DEMETHYLASE
KeywordsOXIDOREDUCTASE / STEROL BIOSYNTHESIS / CHAGAS DISEASE
Function / homology
Function and homology information


sterol 14alpha-demethylase / sterol 14-demethylase activity / sterol biosynthetic process / iron ion binding / heme binding / membrane
Similarity search - Function
: / Cytochrome P450, E-class, group IV / Cytochrome p450 / Cytochrome P450 / Cytochrome P450, conserved site / Cytochrome P450 cysteine heme-iron ligand signature. / Cytochrome P450 / Cytochrome P450 superfamily / Cytochrome P450 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
PROTOPORPHYRIN IX CONTAINING FE / Chem-WVH / Sterol 14-alpha demethylase / Sterol 14-alpha demethylase
Similarity search - Component
Biological speciesTRYPANOSOMA CRUZI (eukaryote)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.04 Å
AuthorsCalvet, C.M. / Vieira, D.F. / Choi, J.Y. / Cameron, M.D. / Gut, J. / Kellar, D. / Siqueira-Neto, J.L. / McKerrow, J.H. / Roush, W.R. / Podust, L.M.
CitationJournal: J.Med.Chem. / Year: 2014
Title: 4-Aminopyridyl-Based Cyp51 Inhibitors as Anti-Trypanosoma Cruzi Drug Leads with Improved Pharmacokinetic Profile and in Vivo Potency.
Authors: Calvet, C.M. / Vieira, D.F. / Choi, J.Y. / Kellar, D. / Cameron, M.D. / Siqueira-Neto, J.L. / Gut, J. / Johnston, J.B. / Lin, L. / Khan, S. / Mckerrow, J.H. / Roush, W.R. / Podust, L.M.
History
DepositionAug 1, 2013Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 20, 2014Provider: repository / Type: Initial release
Revision 1.1Sep 10, 2014Group: Database references
Revision 1.2Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _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_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_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_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 / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: STEROL 14-ALPHA DEMETHYLASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,93518
Polymers53,2871
Non-polymers2,64817
Water2,252125
1
A: STEROL 14-ALPHA DEMETHYLASE
hetero molecules

A: STEROL 14-ALPHA DEMETHYLASE
hetero molecules

A: STEROL 14-ALPHA DEMETHYLASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)167,80554
Polymers159,8603
Non-polymers7,94451
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_565-x+y,-x+1,z1
crystal symmetry operation2_665-y+1,x-y+1,z1
Buried area18170 Å2
ΔGint-547.6 kcal/mol
Surface area51210 Å2
MethodPISA
Unit cell
Length a, b, c (Å)128.528, 128.528, 116.721
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number182
Space group name H-MP6322
Components on special symmetry positions
IDModelComponents
11A-1482-

SO4

21A-1488-

SO4

31A-2007-

HOH

41A-2104-

HOH

51A-2124-

HOH

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein STEROL 14-ALPHA DEMETHYLASE / TC14DM / CYTOCHROME P450 51 / LANOSTEROL 14-ALPHA DEMETHYLASE / CYP51


Mass: 53286.820 Da / Num. of mol.: 1 / Fragment: RESIDUES 32-481
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) TRYPANOSOMA CRUZI (eukaryote) / Plasmid: PCW / Production host: ESCHERICHIA COLI K-12 (bacteria) / Strain (production host): HMS174(DE3)
References: UniProt: Q5I4E1, UniProt: Q7Z1V1*PLUS, sterol 14alpha-demethylase

-
Non-polymers , 5 types, 142 molecules

#2: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#3: Chemical ChemComp-WVH / 4-[4-[2,4-bis(fluoranyl)phenyl]piperazin-1-yl]-2-fluoranyl-N-[(2R)-3-(1H-indol-3-yl)-1-oxidanylidene-1-(pyridin-4-ylamino)propan-2-yl]benzamide


Mass: 598.618 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C33H29F3N6O2
#4: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 13 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 125 / Source method: isolated from a natural source / Formula: H2O

-
Details

Nonpolymer detailsPROTOPORPHYRIN IX CONTAINING FE (HEM): THIOLATE BOND TO CYS 422
Sequence detailsFIRST 32 RESIDUES AT THE N-TERMINUS ARE REPLACED WITH THE MAKKTSSKGKL SEQUENCE, 6XHIS TAG ...FIRST 32 RESIDUES AT THE N-TERMINUS ARE REPLACED WITH THE MAKKTSSKGKL SEQUENCE, 6XHIS TAG ENGINEERED AT THE C- TERMINUS

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.58 Å3/Da / Density % sol: 52.3 % / Description: NONE
Crystal growpH: 5
Details: 0.4 M AMMONIUM SULFATE, 0.1 M BIS-TRIS PH 5.0, 19% PEG 3350

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1.11587
DetectorType: MARRESERCH / Detector: CCD / Date: Jul 26, 2013 / Details: MIRRORS
RadiationMonochromator: SI (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.11587 Å / Relative weight: 1
ReflectionResolution: 2.04→116.72 Å / Num. obs: 36696 / % possible obs: 99.9 % / Observed criterion σ(I): 0.5 / Redundancy: 11 % / Biso Wilson estimate: 42.9 Å2 / Rmerge(I) obs: 0.09 / Net I/σ(I): 14.6
Reflection shellResolution: 2.04→2.15 Å / Redundancy: 7.1 % / Rmerge(I) obs: 1.24 / Mean I/σ(I) obs: 1.5 / % possible all: 99.2

-
Processing

Software
NameVersionClassification
REFMAC5.7.0032refinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2WX2

2wx2


Resolution: 2.04→80.68 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.938 / SU B: 4.764 / SU ML: 0.128 / Cross valid method: THROUGHOUT / ESU R: 0.183 / ESU R Free: 0.175 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.25365 1833 5 %RANDOM
Rwork0.19927 ---
obs0.20195 34827 99.8 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 43.54 Å2
Baniso -1Baniso -2Baniso -3
1--0.13 Å2-0.13 Å20 Å2
2---0.13 Å20 Å2
3---0.43 Å2
Refinement stepCycle: LAST / Resolution: 2.04→80.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3529 0 164 125 3818
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0180.0193786
X-RAY DIFFRACTIONr_bond_other_d0.0010.023575
X-RAY DIFFRACTIONr_angle_refined_deg1.9632.0165146
X-RAY DIFFRACTIONr_angle_other_deg0.95838217
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.4565446
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.61823.333162
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.75715635
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.3581528
X-RAY DIFFRACTIONr_chiral_restr0.1270.2558
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.0214171
X-RAY DIFFRACTIONr_gen_planes_other0.0050.02867
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_it3.8254.0231787
X-RAY DIFFRACTIONr_mcbond_other3.8234.0191786
X-RAY DIFFRACTIONr_mcangle_it5.1496.0142233
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it4.9574.6221998
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
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: 2.04→2.093 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.399 141 -
Rwork0.318 2476 -
obs--98.24 %

+
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