[English] 日本語
Yorodumi
- EMDB-15713: Structure of Complement C5 in Complex with small molecule inhibit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-15713
TitleStructure of Complement C5 in Complex with small molecule inhibitor and CVF
Map data
Sample
  • Complex: Complement C5-Inhibitor-CVF complex
    • Protein or peptide: Cobra venom factor
  • Protein or peptide: Complement C5 beta chain
  • Protein or peptide: Complement C5 alpha chain
  • Ligand: 5-methoxy-2-[[(1~{S})-1-(2-methoxyphenyl)ethyl]carbamoylamino]-4-(4-methylpentoxy)benzoic acid
  • Ligand: MAGNESIUM ION
Function / homology
Function and homology information


Terminal pathway of complement / membrane attack complex / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation, alternative pathway / complement activation / chemokine activity / endopeptidase inhibitor activity / positive regulation of vascular endothelial growth factor production / positive regulation of chemokine production ...Terminal pathway of complement / membrane attack complex / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation, alternative pathway / complement activation / chemokine activity / endopeptidase inhibitor activity / positive regulation of vascular endothelial growth factor production / positive regulation of chemokine production / Peptide ligand-binding receptors / complement activation, classical pathway / Regulation of Complement cascade / chemotaxis / toxin activity / G alpha (i) signalling events / killing of cells of another organism / cell surface receptor signaling pathway / inflammatory response / G protein-coupled receptor signaling pathway / signaling receptor binding / extracellular space / extracellular exosome / extracellular region / metal ion binding
Similarity search - Function
: / Complement component 5, CUB domain / : / : / Complement component 3, CUB domain, second segment / Complement component 3, CUB domain, first segment / Complement C3-like, NTR domain / Alpha-2-macroglobulin, conserved site / Alpha-2-macroglobulin family thiolester region signature. / Complement C3/4/5, macroglobulin domain MG1 ...: / Complement component 5, CUB domain / : / : / Complement component 3, CUB domain, second segment / Complement component 3, CUB domain, first segment / Complement C3-like, NTR domain / Alpha-2-macroglobulin, conserved site / Alpha-2-macroglobulin family thiolester region signature. / Complement C3/4/5, macroglobulin domain MG1 / Macroglobulin domain MG1 / : / Alpha-macro-globulin thiol-ester bond-forming region / Anaphylatoxin, complement system domain / Anaphylatoxin domain signature. / Anaphylatoxin, complement system / Anaphylatoxin/fibulin / Anaphylotoxin-like domain / Anaphylatoxin domain profile. / Anaphylatoxin homologous domain / Netrin C-terminal Domain / Netrin module, non-TIMP type / UNC-6/NTR/C345C module / Alpha-macroglobulin, receptor-binding / Alpha-macroglobulin, receptor-binding domain superfamily / Macroglobulin domain MG4 / Macroglobulin domain MG3 / A-macroglobulin receptor binding domain / Macroglobulin domain MG4 / Macroglobulin domain MG3 / A-macroglobulin receptor / Netrin domain / NTR domain profile. / Tissue inhibitor of metalloproteinases-like, OB-fold / Alpha-2-macroglobulin / Macroglobulin domain / Alpha-2-macroglobulin, bait region domain / Alpha-macroglobulin-like, TED domain / Alpha-2-macroglobulin family / MG2 domain / A-macroglobulin TED domain / Alpha-2-macroglobulin bait region domain / Alpha-2-Macroglobulin / Alpha-2-macroglobulin family / Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid / Immunoglobulin-like fold
Similarity search - Domain/homology
Complement C5 / Cobra venom factor
Similarity search - Component
Biological speciesHomo sapiens (human) / human (human) / monocled cobra (monocled cobra)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.35 Å
AuthorsSrinivas H
Funding support Switzerland, 1 items
OrganizationGrant numberCountry
Other private Switzerland
CitationJournal: Nat Chem Biol / Year: 2019
Title: A small-molecule inhibitor of C5 complement protein.
Authors: Keith Jendza / Mitsunori Kato / Michael Salcius / Honnappa Srinivas / Andrea De Erkenez / Anh Nguyen / Doug McLaughlin / Celine Be / Christian Wiesmann / Jason Murphy / Philippe Bolduc / ...Authors: Keith Jendza / Mitsunori Kato / Michael Salcius / Honnappa Srinivas / Andrea De Erkenez / Anh Nguyen / Doug McLaughlin / Celine Be / Christian Wiesmann / Jason Murphy / Philippe Bolduc / Muneto Mogi / Jose Duca / Abdel Namil / Michael Capparelli / Veronique Darsigny / Erik Meredith / Ritesh Tichkule / Luciana Ferrara / Jessica Heyder / Fang Liu / Patricia A Horton / Michael J Romanowski / Markus Schirle / Nello Mainolfi / Karen Anderson / Gregory A Michaud /
Abstract: The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human complement component 5 protein (C5) is a validated drug target ...The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.
History
DepositionSep 2, 2022-
Header (metadata) releaseDec 21, 2022-
Map releaseDec 21, 2022-
SupersessionApr 19, 2023ID: EMD-4401
UpdateApr 19, 2023-
Current statusApr 19, 2023Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_15713.png

Downloads & links

-
Map

FileDownload / File: emd_15713.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.86 Å
Density
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.118337534 - 0.23124841
Average (Standard dev.)0.00063536013 (±0.006734457)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 258.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_15713_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_15713_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Complement C5-Inhibitor-CVF complex

EntireName: Complement C5-Inhibitor-CVF complex
Components
  • Complex: Complement C5-Inhibitor-CVF complex
    • Protein or peptide: Cobra venom factor
  • Protein or peptide: Complement C5 beta chain
  • Protein or peptide: Complement C5 alpha chain
  • Ligand: 5-methoxy-2-[[(1~{S})-1-(2-methoxyphenyl)ethyl]carbamoylamino]-4-(4-methylpentoxy)benzoic acid
  • Ligand: MAGNESIUM ION

-
Supramolecule #1: Complement C5-Inhibitor-CVF complex

SupramoleculeName: Complement C5-Inhibitor-CVF complex / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 320 KDa

-
Macromolecule #1: Complement C5 beta chain

MacromoleculeName: Complement C5 beta chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: human (human)
Molecular weightTheoretical: 73.615766 KDa
SequenceString: QEQTYVISAP KIFRVGASEN IVIQVYGYTE AFDATISIKS YPDKKFSYSS GHVHLSSENK FQNSAILTIQ PKQLPGGQNP VSYVYLEVV SKHFSKSKRM PITYDNGFLF IHTDKPVYTP DQSVKVRVYS LNDDLKPAKR ETVLTFIDPE GSEVDMVEEI D HIGIISFP ...String:
QEQTYVISAP KIFRVGASEN IVIQVYGYTE AFDATISIKS YPDKKFSYSS GHVHLSSENK FQNSAILTIQ PKQLPGGQNP VSYVYLEVV SKHFSKSKRM PITYDNGFLF IHTDKPVYTP DQSVKVRVYS LNDDLKPAKR ETVLTFIDPE GSEVDMVEEI D HIGIISFP DFKIPSNPRY GMWTIKAKYK EDFSTTGTAY FEVKEYVLPH FSVSIEPEYN FIGYKNFKNF EITIKARYFY NK VVTEADV YITFGIREDL KDDQKEMMQT AMQNTMLING IAQVTFDSET AVKELSYYSL EDLNNKYLYI AVTVIESTGG FSE EAEIPG IKYVLSPYKL NLVATPLFLK PGIPYPIKVQ VKDSLDQLVG GVPVTLNAQT IDVNQETSDL DPSKSVTRVD DGVA SFVLN LPSGVTVLEF NVKTDAPDLP EENQAREGYR AIAYSSLSQS YLYIDWTDNH KALLVGEHLN IIVTPKSPYI DKITH YNYL ILSKGKIIHF GTREKFSDAS YQSINIPVTQ NMVPSSRLLV YYIVTGEQTA ELVSDSVWLN IEEKCGNQLQ VHLSPD ADA YSPGQTVSLN MATGMDSWVA LAAVDSAVYG VQRGAKKPLE RVFQFLEKSD LGCGAGGGLN NANVFHLAGL TFLTNAN AD DSQENDEPCK EILRP

-
Macromolecule #2: Complement C5 alpha chain

MacromoleculeName: Complement C5 alpha chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: human (human)
Molecular weightTheoretical: 112.635008 KDa
SequenceString: TLQKKIEEIA AKYKHSVVKK CCYDGACVNN DETCEQRAAR ISLGPRCIKA FTECCVVASQ LRANISHKDM QLGRLHMKTL LPVSKPEIR SYFPESWLWE VHLVPRRKQL QFALPDSLTT WEIQGVGISN TGICVADTVK AKVFKDVFLE MNIPYSVVRG E QIQLKGTV ...String:
TLQKKIEEIA AKYKHSVVKK CCYDGACVNN DETCEQRAAR ISLGPRCIKA FTECCVVASQ LRANISHKDM QLGRLHMKTL LPVSKPEIR SYFPESWLWE VHLVPRRKQL QFALPDSLTT WEIQGVGISN TGICVADTVK AKVFKDVFLE MNIPYSVVRG E QIQLKGTV YNYRTSGMQF CVKMSAVEGI CTSESPVIDH QGTKSSKCVR QKVEGSSSHL VTFTVLPLEI GLHNINFSLE TW FGKEILV KTLRVVPEGV KRESYSGVTL DPRGIYGTIS RRKEFPYRIP LDLVPKTEIK RILSVKGLLV GEILSAVLSQ EGI NILTHL PKGSAEAELM SVVPVFYVFH YLETGNHWNI FHSDPLIEKQ KLKKKLKEGM LSIMSYRNAD YSYSVWKGGS ASTW LTAFA LRVLGQVNKY VEQNQNSICN SLLWLVENYQ LDNGSFKENS QYQPIKLQGT LPVEARENSL YLTAFTVIGI RKAFD ICPL VKIDTALIKA DNFLLENTLP AQSTFTLAIS AYALSLGDKT HPQFRSIVSA LKREALVKGN PPIYRFWKDN LQHKDS SVP NTGTARMVET TAYALLTSLN LKDINYVNPV IKWLSEEQRY GGGFYSTQDT INAIEGLTEY SLLVKQLRLS MDIDVSY KH KGALHNYKMT DKNFLGRPVE VLLNDDLIVS TGFGSGLATV HVTTVVHKTS TSEEVCSFYL KIDTQDIEAS HYRGYGNS D YKRIVACASY KPSREESSSG SSHAVMDISL PTGISANEED LKALVEGVDQ LFTDYQIKDG HVILQLNSIP SSDFLCVRF RIFELFEVGF LSPATFTVYE YHRPDKQCTM FYSTSNIKIQ KVCEGAACKC VEADCGQMQE ELDLTISAET RKQTACKPEI AYAYKVSIT SITVENVFVK YKATLLDIYK TGEAVAEKDS EITFIKKVTC TNAELVKGRQ YLIMGKEALQ IKYNFSFRYI Y PLDSLTWI EYWPRDTTCS SCQAFLANLD EFAEDIFLNG C

-
Macromolecule #3: Cobra venom factor

MacromoleculeName: Cobra venom factor / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: monocled cobra (monocled cobra)
Molecular weightTheoretical: 184.726734 KDa
SequenceString: MERMALYLVA ALLIGFPGSS HGALYTLITP AVLRTDTEEQ ILVEAHGDST PKQLDIFVHD FPRKQKTLFQ TRVDMNPAGG MLVTPTIEI PAKEVSTDSR QNQYVVVQVT GPQVRLEKVV LLSYQSSFLF IQTDKGIYTP GSPVLYRVFS MDHNTSKMNK T VIVEFQTP ...String:
MERMALYLVA ALLIGFPGSS HGALYTLITP AVLRTDTEEQ ILVEAHGDST PKQLDIFVHD FPRKQKTLFQ TRVDMNPAGG MLVTPTIEI PAKEVSTDSR QNQYVVVQVT GPQVRLEKVV LLSYQSSFLF IQTDKGIYTP GSPVLYRVFS MDHNTSKMNK T VIVEFQTP EGILVSSNSV DLNFFWPYNL PDLVSLGTWR IVAKYEHSPE NYTAYFDVRK YVLPSFEVRL QPSEKFFYID GN ENFHVSI TARYLYGEEV EGVAFVLFGV KIDDAKKSIP DSLTRIPIID GDGKATLKRD TFRSRFPNLN ELVGHTLYAS VTV MTESGS DMVVTEQSGI HIVASPYQIH FTKTPKYFKP GMPYELTVYV TNPDGSPAAH VPVVSEAFHS MGTTLSDGTA KLIL NIPLN AQSLPITVRT NHGDLPRERQ ATKSMTAIAY QTQGGSGNYL HVAITSTEIK PGDNLPVNFN VKGNANSLKQ IKYFT YLIL NKGKIFKVGR QPRRDGQNLV TMNLHITPDL IPSFRFVAYY QVGNNEIVAD SVWVDVKDTC MGTLVVKGDN LIQMPG AAM KIKLEGDPGA RVGLVAVDKA VYVLNDKYKI SQAKIWDTIE KSDFGCTAGS GQNNLGVFED AGLALTTSTN LNTKQRS AA KCPQPANRRR RSSVLLLDSN ASKAAEFQDQ DLRKCCEDVM HENPMGYTCE KRAKYIQEGD ACKAAFLECC RYIKGVRD E NQRESELFLA RDDNEDGFIA DSDIISRSDF PKSWLWLTKD LTEEPNSQGI SSKTMSFYLR DSITTWVVLA VSFTPTKGI CVAEPYEIRV MKVFFIDLQM PYSVVKNEQV EIRAILHNYV NEDIYVRVEL LYNPAFCSAS TKGQRYRQQF PIKALSSRAV PFVIVPLEQ GLHDVEIKAS VQEALWSDGV RKKLKVVPEG VQKSIVTIVK LDPRAKGVGG TQLEVIKARK LDDRVPDTEI E TKIIIQGD PVAQIIENSI DGSKLNHLII TPSGCGEQNM IRMAAPVIAT YYLDTTEQWE TLGINRRTEA VNQIVTGYAQ QM VYKKADH SYAAFTNRAS SSWLTAYVVK VFAMAAKMVA GISHEIICGG VRWLILNRQQ PDGAFKENAP VLSGTMQGGI QGA EEEVYL TAFILVALLE SKTICNDYVN SLDSSIKKAT NYLLKKYEKL QRPYTTALTA YALAAADQLN DDRVLMAAST GRDH WEEYN AHTHNIEGTS YALLALLKMK KFDQTGPIVR WLTDQNFYGE TYGQTQATVM AFQALAEYEI QMPTHKDLNL DITIE LPDR EVPIRYRINY ENALLARTVE TKLNQDITVT ASGDGKATMT ILTFYNAQLQ EKANVCNKFH LNVSVENIHL NAMGAK GAL MLKICTRYLG EVDSTMTIID ISMLTGFLPD AEDLTRLSKG VDRYISRYEV DNNMAQKVAV IIYLNKVSHS EDECLHF KI LKHFEVGFIQ PGSVKVYSYY NLDEKCTKFY HPDKGTGLLN KICIGNVCRC AGETCSSLNH QERIDVPLQI EKACETNV D YVYKTKLLRI EEQDGNDIYV MDVLEVIKQG TDENPRAKTH QYISQRKCQE ALNLKVNDDY LIWGSRSDLL PTKDKISYI ITKNTWIERW PHEDECQEEE FQKLCDDFAQ FSYTLTEFGC PT

-
Macromolecule #4: 5-methoxy-2-[[(1~{S})-1-(2-methoxyphenyl)ethyl]carbamoylamino]-4-...

MacromoleculeName: 5-methoxy-2-[[(1~{S})-1-(2-methoxyphenyl)ethyl]carbamoylamino]-4-(4-methylpentoxy)benzoic acid
type: ligand / ID: 4 / Number of copies: 1 / Formula: H1H
Molecular weightTheoretical: 444.521 Da
Chemical component information

ChemComp-H1H:
5-methoxy-2-[[(1~{S})-1-(2-methoxyphenyl)ethyl]carbamoylamino]-4-(4-methylpentoxy)benzoic acid

-
Macromolecule #5: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 5 / Number of copies: 1 / Formula: MG
Molecular weightTheoretical: 24.305 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5 / Details: 50mM HEPES pH 7.5 100mM NaCl
VitrificationCryogen name: ETHANE
DetailsComplement C5-Inhibitor-CVF complex

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 1.4 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

3pvm

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.35 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 351000
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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