[English] 日本語
Yorodumi
- PDB-6yt1: Mtb TMK crystal structure in complex with compound 26 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6yt1
TitleMtb TMK crystal structure in complex with compound 26
ComponentsThymidylate kinase
KeywordsTRANSFERASE / Kinase activity / Inhibitor complex
Function / homology
Function and homology information


TMP metabolic process / dTMP kinase / dUDP biosynthetic process / dTDP biosynthetic process / dTMP kinase activity / dTTP biosynthetic process / GTP binding / magnesium ion binding / protein homodimerization activity / ATP binding ...TMP metabolic process / dTMP kinase / dUDP biosynthetic process / dTDP biosynthetic process / dTMP kinase activity / dTTP biosynthetic process / GTP binding / magnesium ion binding / protein homodimerization activity / ATP binding / cytoplasm / cytosol
Similarity search - Function
Thymidylate kinase, conserved site / Thymidylate kinase signature. / Thymidylate kinase / Thymidylate kinase-like domain / Thymidylate kinase / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
CITRIC ACID / Chem-PK5 / Thymidylate kinase
Similarity search - Component
Biological speciesMycobacterium tuberculosis H37Rv (bacteria)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsMerceron, R. / De Munck, S. / Jian, Y. / Munier-Lehmann, H. / Van Calenbergh, S. / Savvides, S.N.
CitationJournal: Eur.J.Med.Chem. / Year: 2020
Title: Endeavors towards transformation of M. tuberculosis thymidylate kinase (MtbTMPK) inhibitors into potential antimycobacterial agents.
Authors: Jian, Y. / Merceron, R. / De Munck, S. / Forbes, H.E. / Hulpia, F. / Risseeuw, M.D.P. / Van Hecke, K. / Savvides, S.N. / Munier-Lehmann, H. / Boshoff, H.I.M. / Van Calenbergh, S.
History
DepositionApr 23, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 2, 2020Provider: repository / Type: Initial release
Revision 1.1Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Thymidylate kinase
B: Thymidylate kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,9607
Polymers45,3252
Non-polymers1,6355
Water4,720262
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2630 Å2
ΔGint-5 kcal/mol
Surface area15880 Å2
MethodPISA
Unit cell
Length a, b, c (Å)87.740, 87.740, 112.700
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212
Space group name HallP4nw2abw
Symmetry operation#1: x,y,z
#2: -y+1/2,x+1/2,z+3/4
#3: y+1/2,-x+1/2,z+1/4
#4: x+1/2,-y+1/2,-z+1/4
#5: -x+1/2,y+1/2,-z+3/4
#6: -x,-y,z+1/2
#7: y,x,-z
#8: -y,-x,-z+1/2
Components on special symmetry positions
IDModelComponents
11B-449-

HOH

21B-471-

HOH

31B-509-

HOH

41B-511-

HOH

51B-522-

HOH

61B-527-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-ID
11
21

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11METMETVALVAL(chain 'A' and (resid 1 through 18 or (resid 19...AA1 - 781 - 78
12THRTHRASPASP(chain 'A' and (resid 1 through 18 or (resid 19...AA80 - 9480 - 94
13TYRTYRVALVAL(chain 'A' and (resid 1 through 18 or (resid 19...AA96 - 9796 - 97
14ASNASNLEULEU(chain 'A' and (resid 1 through 18 or (resid 19...AA100 - 128100 - 128
15PROPROVALVAL(chain 'A' and (resid 1 through 18 or (resid 19...AA131 - 141131 - 141
16GLUGLUGLUGLU(chain 'A' and (resid 1 through 18 or (resid 19...AA166166
17ALAALAGLNGLN(chain 'A' and (resid 1 through 18 or (resid 19...AA169 - 172169 - 172
18ARGARGALAALA(chain 'A' and (resid 1 through 18 or (resid 19...AA174 - 183174 - 183
19GLYGLYPROPRO(chain 'A' and (resid 1 through 18 or (resid 19...AA186 - 210186 - 210
110PK5PK5PK5PK5(chain 'A' and (resid 1 through 18 or (resid 19...AC301
111HOHHOHHOHHOH(chain 'A' and (resid 1 through 18 or (resid 19...AH401
212METMETVALVAL(chain 'B' and (resid 1 through 13 or (resid 14...BB1 - 781 - 78
213THRTHRASPASP(chain 'B' and (resid 1 through 13 or (resid 14...BB80 - 9480 - 94
214TYRTYRVALVAL(chain 'B' and (resid 1 through 13 or (resid 14...BB96 - 9796 - 97
215ASNASNLEULEU(chain 'B' and (resid 1 through 13 or (resid 14...BB100 - 128100 - 128
216PROPROVALVAL(chain 'B' and (resid 1 through 13 or (resid 14...BB131 - 141131 - 141
217GLUGLUGLUGLU(chain 'B' and (resid 1 through 13 or (resid 14...BB148148
218ALAALAGLNGLN(chain 'B' and (resid 1 through 13 or (resid 14...BB169 - 172169 - 172
219ARGARGALAALA(chain 'B' and (resid 1 through 13 or (resid 14...BB174 - 183174 - 183
220GLYGLYPROPRO(chain 'B' and (resid 1 through 13 or (resid 14...BB186 - 210186 - 210
221PK5PK5PK5PK5(chain 'B' and (resid 1 through 13 or (resid 14...BE301
222HOHHOHHOHHOH(chain 'B' and (resid 1 through 13 or (resid 14...BI401

-
Components

#1: Protein Thymidylate kinase / Thymidine monophosphate kinase / dTMP kinase / TMPK


Mass: 22662.525 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mycobacterium tuberculosis H37Rv (bacteria)
Gene: tmk, Rv3247c / Production host: Escherichia coli (E. coli) / References: UniProt: P9WKE1, dTMP kinase
#2: Chemical ChemComp-PK5 / 2-ethyl-~{N}-[[4-[4-[5-methyl-2,4-bis(oxidanylidene)pyrimidin-1-yl]piperidin-1-yl]phenyl]methyl]-1,2,3,5,6,7,8,8~{a}-octahydroimidazo[1,2-a]pyridine-3-carboxamide


Mass: 529.074 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H37ClN6O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-CIT / CITRIC ACID


Mass: 192.124 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C6H8O7
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 262 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.39 Å3/Da / Density % sol: 48.59 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.2 M Ammonium tartrate dibasic, 20% w/v Polyethylene glycol 3,350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 7, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionResolution: 1.9→41.7 Å / Num. obs: 35305 / % possible obs: 98.85 % / Redundancy: 13.7 % / Biso Wilson estimate: 27.71 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.109 / Net I/σ(I): 22.1
Reflection shellResolution: 1.9→1.99 Å / Num. unique obs: 5324 / CC1/2: 0.95 / Rrim(I) all: 0.729

-
Processing

Software
NameVersionClassification
BUSTERrefinement
PHENIX1.17.1_3660refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5NRQ

5nrq


Resolution: 1.9→40.88 Å / SU ML: 0.2256 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 22.1596
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2033 1764 5 %
Rwork0.1673 33524 -
obs0.1691 35288 99.82 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 36.17 Å2
Refinement stepCycle: LAST / Resolution: 1.9→40.88 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2793 0 98 262 3153
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0072998
X-RAY DIFFRACTIONf_angle_d0.72894098
X-RAY DIFFRACTIONf_chiral_restr0.0461451
X-RAY DIFFRACTIONf_plane_restr0.0046581
X-RAY DIFFRACTIONf_dihedral_angle_d18.46541067
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9-1.950.40971350.35342549X-RAY DIFFRACTION99.78
1.95-2.010.25991320.23132508X-RAY DIFFRACTION99.89
2.01-2.070.23161330.18412552X-RAY DIFFRACTION99.93
2.07-2.150.21331320.16612535X-RAY DIFFRACTION99.96
2.15-2.230.24181330.19452518X-RAY DIFFRACTION98.95
2.23-2.340.30691340.21412538X-RAY DIFFRACTION99.4
2.34-2.460.18311350.15282564X-RAY DIFFRACTION100
2.46-2.610.18371340.14382543X-RAY DIFFRACTION100
2.61-2.810.18941360.15272589X-RAY DIFFRACTION99.96
2.81-3.10.22361360.1522592X-RAY DIFFRACTION100
3.1-3.540.17371370.15392600X-RAY DIFFRACTION99.96
3.55-4.470.16941400.13832652X-RAY DIFFRACTION99.96
4.47-40.880.1921470.17442784X-RAY DIFFRACTION99.83
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)
19.19317190279-2.72282578672-4.364807847632.742152548081.678498557336.491135401220.0245753639782-0.7306117652420.4635753036530.2887786213260.219206790639-0.202929343202-0.1926653026230.595393369594-0.2376828968550.394562251403-0.03065998796440.05719968025550.251229210317-0.01178033141590.29649546340293.277055916543.1275010065134.593360013
27.59438377707-4.21895365426-3.819440089133.274733660723.429036190564.096186713460.0170439625738-0.5919763926170.4051456447180.2706694890780.172640249889-0.353769861883-0.2398052573820.063640510825-0.1598398340390.3224373135340.002258454459570.06384567105870.283823548934-0.03625858224170.16617136007288.266427126334.0786353687136.727042661
34.37017416978-3.6514307748-2.638445096894.241207617692.141748685762.69016319832-0.030358200216-0.127892226171-0.199400374790.214292230665-0.03368607810930.1718704350380.00596579792744-0.03864394142410.1437223802730.228185038125-0.06157835510560.02789430143470.2074770107190.01350083089740.18867876252293.932337688323.4218800852129.350541173
44.17666390654-4.16853503882-6.022825078764.667002719595.864776105798.699514358030.146774581672-0.05337354137980.167841592051-0.01200052267710.00632357226483-0.110794636724-0.237802655550.0326412552871-0.4577266583550.250548861816-0.02890328399950.0289190231070.1795450405410.03842756567490.21053664765594.062109387634.4780604095127.77560825
53.845122669364.70323502583-4.529756945898.30658759193-3.182945977257.65405020273-0.2399060583610.4807598039120.153618976233-0.357255536680.345702342550.1339423910760.01609738945080.0117601879782-0.1348998379230.219132896438-0.01889257596620.03404035070780.236275953239-0.02389314988750.17232303829797.555616805629.1221274556114.756278374
65.5644791017-1.57163354829-1.242518519.050239391891.59662279744.27544969223-0.0364950133720.0515612707646-0.569956569963-0.101964441841-0.1012247597051.02431202933-0.188485175796-0.4060435020750.03332254747680.204791154691-0.004316026228080.02963517442360.3292519444130.008973977608960.29454670283484.993638995331.3803053453121.279613218
74.94695902043-1.4250333914-0.3507726265764.93438527696-0.2804660642982.135446542420.0151832639382-0.1943320135850.2825968918340.43843791712-0.00484067489279-0.438841903228-0.1805121807890.311968904577-0.05550591222440.294489966508-0.07732299450960.02169259355170.2145731342040.009792394894680.247165817956101.83220214139.4529696085124.533545341
87.55754586322-6.08415497277-4.54342807156.546374027245.300035750626.426395409080.672242489789-0.5490358590610.939441725785-0.172540236579-0.3564194950230.749146546845-0.488606840422-0.643760202921-0.3467532355560.7001353707220.04547896671170.1954439263730.332992938315-0.03041512153950.64406506899887.682322448453.0932607285130.97290183
96.130203495931.84006520541-4.348484836572.99928748525-0.5356122402756.11445061148-0.2441016599610.321425275528-0.183139635158-0.0677316592160.2101441378270.242677823730.584863588314-0.632537292946-0.06815983608070.307603715044-0.0631839200181-0.01695635671950.2751012766940.06187608728360.22738805005583.0145410058-8.52139234667123.795304533
105.808493707123.7847835471-2.304318933374.00797428798-2.538675582414.18885262623-0.0407171581116-0.04015057700350.0155414754428-0.1881001941730.09037053415090.1440483186490.226789309137-0.312826298282-0.02367759735350.1968221999440.02219459119490.00622740213710.221816267141-0.02074802272120.14781182962187.42038405718.11318711959120.684296282
112.546697311181.14049445255-0.6156862957342.40859645302-0.8107721292873.062367382710.159042764632-0.20942873655-0.0332382390010.239826290822-0.123626013910.03726251039960.0278113397362-0.0880699105152-0.0276106270560.238846538541-0.0017753208373-0.007039662582160.2542305473830.02993906214750.14742674842192.01477068083.90265599292129.470443572
122.78302013720.540786779159-1.587472037533.829758059731.055637612014.03363189010.1737794789580.123351261984-0.224931520945-0.199537967895-0.182848988602-0.3668278327050.192509131807-0.0142371958195-0.01671070675950.2985037879290.086647220492-0.03783633709640.2961099498160.1012289134940.26191931631796.1138615091-4.57176424486124.571932806
134.568309298642.19503885216-2.298051932223.76645823723-1.085968908494.51355764041-0.0375504859354-0.219302276122-0.280117184406-0.00135285393701-0.0753904229758-0.1520413283790.7284185605710.2860362242340.1411306398560.3543072435930.0829254180768-0.02199797771560.2352512554530.0554290760290.29083170408997.2276993214-9.08789973686126.772574216
143.51924580653-2.287262817653.715667705625.78045030492-3.185629820524.05690886850.0287314602443-0.559710227983-1.287286298180.8490917276130.1666339236561.050393462431.40592797797-1.09555017803-0.00582002703380.670457753543-0.1871287980040.0689007782690.3832779890550.08422425326880.48111383428181.1137218466-17.9023306834131.800933725
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 1 through 26 )
2X-RAY DIFFRACTION2chain 'A' and (resid 27 through 42 )
3X-RAY DIFFRACTION3chain 'A' and (resid 43 through 87 )
4X-RAY DIFFRACTION4chain 'A' and (resid 88 through 107 )
5X-RAY DIFFRACTION5chain 'A' and (resid 108 through 124 )
6X-RAY DIFFRACTION6chain 'A' and (resid 125 through 134 )
7X-RAY DIFFRACTION7chain 'A' and (resid 135 through 199 )
8X-RAY DIFFRACTION8chain 'A' and (resid 200 through 210 )
9X-RAY DIFFRACTION9chain 'B' and (resid 1 through 26 )
10X-RAY DIFFRACTION10chain 'B' and (resid 27 through 62 )
11X-RAY DIFFRACTION11chain 'B' and (resid 63 through 124 )
12X-RAY DIFFRACTION12chain 'B' and (resid 125 through 170 )
13X-RAY DIFFRACTION13chain 'B' and (resid 171 through 199 )
14X-RAY DIFFRACTION14chain 'B' and (resid 200 through 210 )

+
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