[English] 日本語
Yorodumi
- PDB-7kyy: Crystal structure of Plasmodium falciparum dihydroorotate dehydro... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7kyy
TitleCrystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM697 (3-methyl-N-(1-(5-methylisoxazol-3-yl)ethyl)-4-(6-(trifluoromethyl)-1H-indol-3-yl)-1H-pyrrole-2-carboxamide)
ComponentsDihydroorotate dehydrogenase (quinone), mitochondrial
KeywordsOXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / Alpha-Beta Barrel / OXIDOREDUCTASE / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex
Function / homology
Function and homology information


Pyrimidine biosynthesis / pyrimidine ribonucleotide biosynthetic process / dihydroorotate dehydrogenase (quinone) activity / dihydroorotate dehydrogenase (quinone) / dihydroorotate dehydrogenase activity / 'de novo' UMP biosynthetic process / 'de novo' pyrimidine nucleobase biosynthetic process / mitochondrial inner membrane / plasma membrane
Similarity search - Function
Dihydroorotate dehydrogenase, class 2 / Dihydroorotate dehydrogenase signature 1. / Dihydroorotate dehydrogenase signature 2. / Dihydroorotate dehydrogenase, conserved site / Dihydroorotate dehydrogenase domain / Dihydroorotate dehydrogenase / Aldolase-type TIM barrel
Similarity search - Domain/homology
FLAVIN MONONUCLEOTIDE / OROTIC ACID / Chem-XCD / Dihydroorotate dehydrogenase (quinone), mitochondrial
Similarity search - Component
Biological speciesPlasmodium falciparum (malaria parasite P. falciparum)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsDeng, X. / Phillips, M. / Tomchick, D.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI103947 United States
CitationJournal: J.Med.Chem. / Year: 2021
Title: Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series.
Authors: Palmer, M.J. / Deng, X. / Watts, S. / Krilov, G. / Gerasyuto, A. / Kokkonda, S. / El Mazouni, F. / White, J. / White, K.L. / Striepen, J. / Bath, J. / Schindler, K.A. / Yeo, T. / ...Authors: Palmer, M.J. / Deng, X. / Watts, S. / Krilov, G. / Gerasyuto, A. / Kokkonda, S. / El Mazouni, F. / White, J. / White, K.L. / Striepen, J. / Bath, J. / Schindler, K.A. / Yeo, T. / Shackleford, D.M. / Mok, S. / Deni, I. / Lawong, A. / Huang, A. / Chen, G. / Wang, W. / Jayaseelan, J. / Katneni, K. / Patil, R. / Saunders, J. / Shahi, S.P. / Chittimalla, R. / Angulo-Barturen, I. / Jimenez-Diaz, M.B. / Wittlin, S. / Tumwebaze, P.K. / Rosenthal, P.J. / Cooper, R.A. / Aguiar, A.C.C. / Guido, R.V.C. / Pereira, D.B. / Mittal, N. / Winzeler, E.A. / Tomchick, D.R. / Laleu, B. / Burrows, J.N. / Rathod, P.K. / Fidock, D.A. / Charman, S.A. / Phillips, M.A.
History
DepositionDec 9, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 19, 2021Provider: repository / Type: Initial release
Revision 1.1Dec 8, 2021Group: Database references / Category: 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 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dihydroorotate dehydrogenase (quinone), mitochondrial
B: Dihydroorotate dehydrogenase (quinone), mitochondrial
C: Dihydroorotate dehydrogenase (quinone), mitochondrial
D: Dihydroorotate dehydrogenase (quinone), mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)185,65916
Polymers181,5444
Non-polymers4,11512
Water8,755486
1
A: Dihydroorotate dehydrogenase (quinone), mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,4154
Polymers45,3861
Non-polymers1,0293
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Dihydroorotate dehydrogenase (quinone), mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,4154
Polymers45,3861
Non-polymers1,0293
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Dihydroorotate dehydrogenase (quinone), mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,4154
Polymers45,3861
Non-polymers1,0293
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
4
D: Dihydroorotate dehydrogenase (quinone), mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,4154
Polymers45,3861
Non-polymers1,0293
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)93.061, 97.254, 186.882
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein
Dihydroorotate dehydrogenase (quinone), mitochondrial / DHOdehase / Dihydroorotate oxidase


Mass: 45385.914 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum (isolate 3D7) (eukaryote)
Strain: isolate 3D7 / Gene: PFF0160c / Plasmid: pET28b / Production host: Escherichia coli (E. coli) / Strain (production host): DE3
References: UniProt: Q08210, dihydroorotate dehydrogenase (quinone)
#2: Chemical
ChemComp-XCD / 3-methyl-N-[(1R)-1-(5-methyl-1,2-oxazol-3-yl)ethyl]-4-[6-(trifluoromethyl)-1H-indol-3-yl]-1H-pyrrole-2-carboxamide


Mass: 416.396 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H19F3N4O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-FMN / FLAVIN MONONUCLEOTIDE / RIBOFLAVIN MONOPHOSPHATE


Mass: 456.344 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C17H21N4O9P / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-ORO / OROTIC ACID


Mass: 156.096 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C5H4N2O4 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 486 / 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: 2.28 Å3/Da / Density % sol: 46.1 % / Description: prism
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 85 mM HEPES pH 7.5, 2-propanol 8.5%, 17% PEG 4000, 15% v/v Glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97895 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 13, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97895 Å / Relative weight: 1
ReflectionResolution: 2→47.06 Å / Num. obs: 115187 / % possible obs: 99.7 % / Redundancy: 7.2 % / Biso Wilson estimate: 21.37 Å2 / Rpim(I) all: 0.044 / Net I/σ(I): 17.55
Reflection shellResolution: 2→2.03 Å / Redundancy: 6.5 % / Mean I/σ(I) obs: 1.43 / Num. unique obs: 5586 / Rpim(I) all: 0.542 / % possible all: 98.3

-
Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3I65

3i65


Resolution: 2→47.06 Å / SU ML: 0.1785 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 19.7361
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2069 1008 1 %
Rwork0.1627 100166 -
obs0.1631 101174 87.68 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 30.65 Å2
Refinement stepCycle: LAST / Resolution: 2→47.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms11749 0 288 486 12523
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.008412281
X-RAY DIFFRACTIONf_angle_d0.906216585
X-RAY DIFFRACTIONf_chiral_restr0.05051834
X-RAY DIFFRACTIONf_plane_restr0.00552092
X-RAY DIFFRACTIONf_dihedral_angle_d19.28264580
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2-2.10.2352880.18038452X-RAY DIFFRACTION52.43
2.1-2.240.19531120.166911377X-RAY DIFFRACTION70.46
2.24-2.410.21431450.172614839X-RAY DIFFRACTION91.72
2.41-2.650.23771610.166616150X-RAY DIFFRACTION99.42
2.65-3.030.21821730.167416268X-RAY DIFFRACTION99.85
3.03-3.820.2011650.158516317X-RAY DIFFRACTION99.67
3.82-47.060.18991640.156416763X-RAY DIFFRACTION99.33
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)
14.591473620580.745551585986-0.6910274296593.56336458785-0.4353805966985.034617056060.1326380381410.02064439414970.01793549175030.188561263041-0.0558522255441-0.288328698832-0.2533284500910.552593814799-0.13928599950.1317662691150.0169448681861-0.06248765845560.2815166602070.02309308707310.227580370089-7.925764226977.52535894895-10.2304409439
22.29554305857-0.1223494974160.3047301630221.708964307330.4934371872662.740476809030.000655833970882-0.207871379494-0.2387191617480.2277647293260.02824511252-0.07328469829620.314325309053-0.0262971540865-0.03564230638560.20436983234-0.0114815501722-0.01190949500760.1195255383240.04051844968170.113559246504-24.28366206781.07944996057-13.0858082834
32.438454366370.4354996489030.4750226321411.890044937210.05276310584892.421419514280.06584441757580.178005266286-0.1993655100670.02829948464570.0249960267376-0.07219290873970.2335684304570.0266102702118-0.04557194572050.149423122819-0.03051471384960.001770583433110.100617481024-0.007710247193940.0657296302645-29.9737555806-1.96918552667-24.6538039917
42.48333535184-0.2186739462960.453375944881.287556422410.3894781509452.4463714941-0.0928119083797-0.1150624087680.3842526197950.1316446394370.02378128749950.0208503798068-0.404080858481-0.07047976968710.02565473260650.209739264686-0.0156540502570.001509224228060.07674468005150.004941433045750.138446437251-30.993476964116.2247050714-16.878568957
54.442479795060.8369873250930.08386014897582.35634274582-0.5083215424571.10958204013-0.02509909466760.2367706768890.0765291862209-0.587258203912-0.145834911516-0.3067225399070.3496169041170.5812902932490.1636105684560.3402367720020.0423555367910.05143949833770.5152635816820.09648249387580.181318833359-6.04200942208-2.7569340844711.8524996119
61.90199220441-0.04371690834030.05587947102952.58402210984-0.3662772825192.127898217830.004012888616920.2881671072930.14698972546-0.196692100603-0.05748163527490.0701710771017-0.02787229881190.2282801104730.04248851150.1605223415640.0161858912144-0.03914697954790.1227347316510.03327085234820.0767772307896-21.8695785766-0.83282422696319.6017800715
72.5963003211-0.618338626356-0.05257794268992.23443206356-0.3309430773041.9381662162-0.02677622334920.04367490999870.3732074772910.0200853594074-0.0928566589231-0.283470218912-0.4521119032580.6092622165860.04043245397640.204909477414-0.134619901771-0.05848604655540.1973799255650.0654981817850.157211525838-13.62147930398.0976649542128.3870080768
82.8520047232-0.9312821898251.468586940754.67581330622-2.899099073255.52979996831-0.320921850963-0.4984607502360.5006057528730.4236918979010.3263309992450.150609636022-0.823378879609-0.5370715227350.03208261023420.309250096712-0.000913668397566-0.01577664304060.153198921962-0.02818839460390.194855639473-27.150996742712.287781646139.7559101723
92.19019784946-0.193935023910.4890087106972.0750921082-0.9227024133062.90413801160.0108144695773-0.1735186784640.1158852789490.0822877793892-0.0003525193618090.114287818729-0.1622794875750.125382734358-0.04509208474740.122067800838-0.0305336482367-0.01384813468950.0795778072524-0.03930595576170.094176108223-25.30479504412.7050820553636.1743014221
105.7588368791-1.140557019960.2978468108532.10363854815-0.2118197494051.41824520552-0.269796692542-0.216596555975-0.5126012770470.581486206330.0276489297914-0.122208145740.1048637013630.654100650427-0.03541494643090.1096296386940.0568837630594-0.1350706188820.4012815365040.1011631461310.0821647650892-8.71775049628-6.5260225334836.2162741892
112.40200468239-0.158329970343-0.04757153734361.660092522230.03935054007931.85784023528-0.00390339844448-0.0729886987049-0.336782546784-0.0972043539361-0.1115601091920.04046084270370.2244178865180.3202826846540.09305386322190.1340506232330.0480150768314-0.03151575931630.1000024726360.02355989578760.0989904142912-18.5073256947-11.190925034530.0353441953
123.730195200292.02560030614-1.14396163363.96598115623-1.21371329152.13756737449-0.09146528438770.3396599759-0.245908141614-0.3994432594860.1216921090740.2958576389240.479067147311-0.04617155902550.01040031482560.196044367470.0322709094513-0.084952157830.102837674596-0.03057390685840.188554711874-26.7885175423-17.613475175920.7393809871
134.412665687820.267885447991-0.2298017604632.33841256587-0.364150545472.18125614674-0.0589274306622-0.0463539819745-0.322664697481-0.2077478927060.2600279150130.4685557478760.154958949304-0.523304298141-0.13993721480.198036907612-0.017738365434-0.07569365818190.2806298808880.06700673795860.300198836051-68.51851116784.799957758457.92821903594
142.53014462164-0.7819355819710.9407542394641.68728051470.1115534358242.15097290865-0.0209443959404-0.700098316728-0.3671858301540.3530408268140.2162193171740.4959009347650.14714266198-1.02373517533-0.305612636310.2536485022270.05533129145820.01214082913960.5648930604890.2032138188760.430365140515-71.73609912911.4674512285725.400087934
153.62168028054-0.05984677241541.695366936422.25269214684-0.6781412623144.334969498470.125744499379-0.590808602159-0.5353635662050.1111488820150.06333811538960.08023366502740.43069785974-0.265318426305-0.1043612340770.2558673876820.0141161105226-0.06940368756690.2499451326560.1162241594830.368010918245-55.2304838082-7.4583059707320.0956423011
163.8980400333-0.5837752503940.6195530619971.87082417778-0.4147054124451.24506940577-0.0228064726257-0.8844650300620.1424071301030.241188071840.1774708726250.0132264243952-0.213338147154-0.27573737959-0.1417971079020.2257181547760.104043053772-0.01677785215860.4269403598980.02132781868920.19590558395-55.92192499748.1141511110127.2427497201
172.243592266280.008350822800960.2441556144771.3723681695-0.7349373338282.8643189806-0.149388883653-0.2186160699630.3282873232890.08954364757930.1357961061340.0449670389322-0.44119041833-0.1562260485840.008919399131110.2217477648890.0599569332046-0.0475725787450.148664316395-0.03353666891530.258282670207-56.675723780316.908215432714.4828691111
182.67742227927-0.312101900218-4.315599060188.89427750516-1.430276047167.38497330720.246068498969-0.436276279461-0.04785220383221.24410539407-0.1905296711850.0915104861180.154506577370.2025632442-0.03946688702670.374738799911-0.05372216174090.06216766984150.509943262213-0.0588025458090.563169878225-84.7241624022-9.26027207918-10.1048564081
193.263752971840.21904287466-0.8495672403032.428953908550.314167796682.00023140410.001470900780320.7691282304550.29113956313-0.416821249052-0.08224379296160.202335648453-0.229305262097-0.5843791086470.06069291418790.1994672912610.067558887838-0.08838443248120.3028965151120.06350811815540.225248848862-70.2007363543-0.327929629708-30.5198503826
203.04767154893-0.746084074986-0.4427300232453.057439519810.5717383755981.74820309963-0.1720835500750.0214900502024-0.3131232102130.0864597783720.029796580208-0.02922456917740.245559499577-0.1126043132970.1337791870640.158045285883-0.05082249163760.005146773174990.0825080097594-0.02782648242360.266212825544-64.8366084298-16.8408520578-20.4928687417
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'A' and (resid -2 through 193 )AA-2 - 1931 - 38
22chain 'A' and (resid 194 through 262 )AA194 - 26239 - 107
33chain 'A' and (resid 263 through 474 )AA263 - 474108 - 283
44chain 'A' and (resid 475 through 567 )AA475 - 567284 - 376
55chain 'B' and (resid 167 through 205 )BE167 - 2051 - 39
66chain 'B' and (resid 206 through 247 )BE206 - 24740 - 83
77chain 'B' and (resid 248 through 356 )BE248 - 35684 - 192
88chain 'B' and (resid 357 through 376 )BE357 - 376193 - 212
99chain 'B' and (resid 377 through 448 )BE377 - 448213 - 250
1010chain 'B' and (resid 449 through 474 )BE449 - 474251 - 276
1111chain 'B' and (resid 475 through 537 )BE475 - 537277 - 339
1212chain 'B' and (resid 538 through 566 )BE538 - 566340 - 368
1313chain 'C' and (resid 160 through 247 )CI160 - 2471 - 91
1414chain 'C' and (resid 248 through 282 )CI248 - 28292 - 126
1515chain 'C' and (resid 283 through 418 )CI283 - 418127 - 226
1616chain 'C' and (resid 419 through 474 )CI419 - 474227 - 282
1717chain 'C' and (resid 475 through 567 )CI475 - 567283 - 377
1818chain 'D' and (resid 161 through 178 )DM161 - 1781 - 18
1919chain 'D' and (resid 179 through 528 )DM179 - 52819 - 335
2020chain 'D' and (resid 529 through 566 )DM529 - 566336 - 373

+
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://pdbjlvh1.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