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- EMDB-62461: Polymerase complex-inhibitor IERDRP-0519-bound measles virus L-P ... -
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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Polymerase complex-inhibitor IERDRP-0519-bound measles virus L-P complex | |||||||||
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![]() | Complex / Transcription | |||||||||
Function / homology | ![]() NNS virus cap methyltransferase / GDP polyribonucleotidyltransferase / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / viral genome replication / virion component / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / RNA-directed RNA polymerase / RNA-directed RNA polymerase activity / GTPase activity ...NNS virus cap methyltransferase / GDP polyribonucleotidyltransferase / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / viral genome replication / virion component / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / RNA-directed RNA polymerase / RNA-directed RNA polymerase activity / GTPase activity / DNA-templated transcription / RNA binding / ATP binding Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Wang YR / Zhang HQ | |||||||||
Funding support | 1 items
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![]() | ![]() Title: Structures of the measles virus polymerase complex with non-nucleoside inhibitors and mechanism of inhibition. Authors: Yiru Wang / Lixia Zhao / Yi Zhang / Xiuxia Gao / Yannan Wang / Wenping Shi / Roger D Kornberg / Heqiao Zhang / ![]() ![]() Abstract: The measles virus (MeV), a highly contagious non-segmented negative-sense RNA virus in the Paramyxoviridae family, causes millions of infections annually, with no approved antivirals available. The ...The measles virus (MeV), a highly contagious non-segmented negative-sense RNA virus in the Paramyxoviridae family, causes millions of infections annually, with no approved antivirals available. The viral polymerase complex, comprising the large (L) protein and the tetrameric phosphoprotein (P), is a key antiviral target. We determined the cryo-electron microscopy structures of the MeV polymerase complex alone and bound to two non-nucleoside inhibitors, ERDRP-0519 and AS-136A. Inhibitor binding induces a conformational change in the catalytic loop, allosterically locking the polymerase in an inactive "GDN-out" state. These findings led to the proposal that ERDRP-0519 would also be effective against Nipah virus (NiV), a highly pathogenic virus with no available antivirals. This proposal was confirmed by structure determination of the NiV polymerase complex and by inhibition of transcription. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 42.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.7 KB 17.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.2 KB | Display | ![]() |
Images | ![]() | 44.3 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
Others | ![]() ![]() | 77.8 MB 77.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 17 KB | Display | |
Data in CIF | ![]() | 21.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9kntMC ![]() 9knqC ![]() 9knvC ![]() 9knzC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.9643 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_62461_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_62461_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Polymerase complex
Entire | Name: Polymerase complex |
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Components |
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-Supramolecule #1: Polymerase complex
Supramolecule | Name: Polymerase complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: RNA-directed RNA polymerase L
Macromolecule | Name: RNA-directed RNA polymerase L / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: RNA-directed RNA polymerase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 248.056953 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDSLSVNQIL YPEVHLDSPI VTNKIVAILE YARVPHAYSL EDPTLCQNIK HRLKNGFSNQ MIINNVEVGN VIKSKLRSYP AHSHIPYPN CNQDLFNIED KESTRKIREL LKKGNSLYSK VSDKVFQCLR DTNSRLGLGS ELREDIKEKI INLGVYMHSS Q WFEPFLFW ...String: MDSLSVNQIL YPEVHLDSPI VTNKIVAILE YARVPHAYSL EDPTLCQNIK HRLKNGFSNQ MIINNVEVGN VIKSKLRSYP AHSHIPYPN CNQDLFNIED KESTRKIREL LKKGNSLYSK VSDKVFQCLR DTNSRLGLGS ELREDIKEKI INLGVYMHSS Q WFEPFLFW FTVKTEMRSV IKSQTHTCHR RRHTPVFFTG SSVELLISRD LVAIISKESQ HVYYLTFELV LMYCDVIEGR LM TETAMTI DARYAELLGR VRYMWKLIDG FFPALGNPTY QIVAMLEPLS LAYLQLRDIT VELRGAFLNH CFTEIHDVLD QNG FSDEGT YHELIEALDY IFITDDIHLT GEIFSFFRSF GHPRLEAVTA AENVRKYMNQ PKVIVYETLM KGHAIFCGII INGY RDRHG GSWPPLTLPL HAADTIRNAQ ASGEGLTHEQ CVDNWKSFAG VRFGCFMPLS LDSDLTMYLK DKALAALQRE WDSVY PKEF LRYDPPKGTG SRRLVDVFLN DSSFDPYDMI MYVVSGAYLH DPEFNLSYSL KEKEIKETGR LFAKMTYKMR ACQVIA ENL ISNGIGKYFK DNGMAKDEHD LTKALHTLAV SGVPKDLKES HRGGPVLKTY SRSPVHTSTR NVKAEKGFVG FPHVIRQ NQ DTDHPENIET YETVSAFITT DLKKYCLNWR YETISLFAQR LNEIYGLPSF FQWLHKRLET SVLYVSDPHC PPDLDAHV P LCKVPNDQIF IKYPMGGIEG YCQKLWTIST IPYLYLAAYE SGVRIASLVQ GDNQTIAVTK RVPSTWPYNL KKREAARVT RDYFVILRQR LHDIGHHLKA NETIVSSHFF VYSKGIYYDG LLVSQSLKSI ARCVFWSETI VDETRAACSN IATTMAKSIE RGYDRYLAY SLNVLKVIQQ ILISLGFTIN STMTRDVVIP LLTNNDLLIR MALLPAPIGG MNYLNMSRLF VRNIGDPVTS S IADLKRMI LASLMPEETL HQVMTQQPGD SSFLDWASDP YSANLVCVQS ITRLLKNITA RFVLIHSPNP MLKGLFHDDS KE EDERLAA FLMDRHIIVP RAAHEILDHS VTGARESIAG MLDTTKGLIR ASMRKGGLTS RVITRLSNYD YEQFRAGMVL LTG RKRNVL IDKESCSVQL ARALRSHMWA RLARGRPIYG LEVPDVLESM RGHLIRRHET CVICECGSVN YGWFFVPSGC QLDD IDKET SSLRVPYIGS TTDERTDMKL AFVRAPSRSL RSAVRIATVY SWAYGDDDSS WNEAWLLARQ RANVSLEELR VITPI STST NLAHRLRDRS TQVKYSGTSL VRVARYTTIS NDNLSFVISD KKVDTNFIYQ QGMLLGLGVL ETLFRLEKDT GSSNTV LHL HVETDCCVIP MIDHPRIPSS RKLELRAELC TNPLIYDNAP LIDRDATRLY TQSHRRHLVE FVTWSTPQLY HILAKST AL SMIDLVTKFE KDHMNEISAL IGDDDINSFI TEFLLIEPRL FTIYLGQCAA INWAFDVHYH RPSGKYQMGE LLSSFLSR M SKGVFKVLVN ALSHPKIYKK FWHCGIIEPI HGPSLDAQNL HTTVCNMVYT CYMTYLDLLL NEELEEFTFL LCESDEDVV PDRFDNIQAK HLCVLADLYC QPGTCPPIRG LRPVEKCAVL TDHIKAEARL SPAGSSWNIN PIIVDHYSCS LTYLRRGSIK QIRLRVDPG FIFDALAEVN VSQPKVGSNN ISNMSIKDFR PPHDDVAKLL KDINTSKHNL PISGGSLANY EIHAFRRIGL N SSACYKAV EISTLIRRCL EPGEDGLFLG EGSGSMLITY KEILKLNKCF YNSGVSANSR SGQRELAPYP SEVGLVEHRM GV GNIVKVL FNGRPEVTWV GSIDCFNFIV SNIPTSSVGF IHSDIETLPN KDTIEKLEEL AAILSMALLL GKIGSILVIK LMP FSGDFV QGFISYVGSH YREVNLVYPR YSNFISTESY LVMTDLKANR LMNPEKIKQQ IIESSVRTSP GLIGHILSIK QLSC IQAIV GGAVSRGDIN PILKKLTPIE QVLISCGLAI NGPKLCKELI HHDVASGQDG LLNSILILYR ELARFKDNQR SQQGM FHAY PVLVSSRQRE LVSRITRKFW GHILLYSGNR KLINRFIQNL KSGYLVLDLH QNIFVKNLSK SEKQIIMTGG LKREWV FKV TVKETKEWYK LVGYSALIKD UniProtKB: RNA-directed RNA polymerase L |
-Macromolecule #2: Phosphoprotein
Macromolecule | Name: Phosphoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 53.961113 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAEEQARHVK NGLECIRALK AEPIGSLAVE EAMAAWSEIS DNPGQDRATC KEEEAGSSGL SKPCLSAIGS TEGGAPRIRG QGSGESDDD AETLGIPSRN LQASSTGLQC YHVYDHSGEA VKGIQDADSI MVQSGLDGDS TLSGGDDESE NSDVDIGEPD T EGYAITDR ...String: MAEEQARHVK NGLECIRALK AEPIGSLAVE EAMAAWSEIS DNPGQDRATC KEEEAGSSGL SKPCLSAIGS TEGGAPRIRG QGSGESDDD AETLGIPSRN LQASSTGLQC YHVYDHSGEA VKGIQDADSI MVQSGLDGDS TLSGGDDESE NSDVDIGEPD T EGYAITDR GSAPISMGFR ASDVETAEGG EIHELLKLQS RGNNFPKLGK TLNVPPPPNP SRASTSETPI KKGTDARLAS FG TEIASLL TGGATQCARK SPSEPSGPGA PAGNVPECVS NAALIQEWTP ESGTTISPRS QNNEEGGDYY DDELFSDVQD IKT ALAKIH EDNQKIISKL ESLLLLKGEV ESIKKQINRQ NISISTLEGH LSSIMIAIPG LGKDPNDPTA DVELNPDLKP IIGR DSGRA LAEVLKKPVA SRQLQGMTNG RTSSRGQLLK EFQLKPIGKK VSSAVGFVPD TGPASRSVIR SIIKSSRLEE DRKRY LMTL LDDIKGANDL AKFHQMLMKI IMK UniProtKB: Phosphoprotein |
-Macromolecule #3: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #4: 2-methyl-~{N}-[4-[(2~{S})-2-(2-morpholin-4-ylethyl)piperidin-1-yl...
Macromolecule | Name: 2-methyl-~{N}-[4-[(2~{S})-2-(2-morpholin-4-ylethyl)piperidin-1-yl]sulfonylphenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide type: ligand / ID: 4 / Number of copies: 1 / Formula: A1EF9 |
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Molecular weight | Theoretical: 529.576 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |