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- EMDB-22283: cryo-EM of human GLP-1R bound to non-peptide agonist LY3502970 -

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Basic information

Entry
Database: EMDB / ID: EMD-22283
Titlecryo-EM of human GLP-1R bound to non-peptide agonist LY3502970
Map data
Sample
  • Complex: Cryo-EM structure of the Glucagon-like peptide-1 receptor in complex with G protein and a non-peptide agonist LY3502970
    • Complex: Glucagon-like peptide 1 receptor
      • Protein or peptide: Glucagon-like peptide 1 receptor
    • Complex: Trimeric stimulatory G protein
      • Protein or peptide: Alpha subunit of Gs with N-terminus swapped with equivalent residues in Gi,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Complex: Nanobody 35
      • Protein or peptide: Nanobody 35
    • Complex: Single-chain variable fragment 16
      • Protein or peptide: single-chain variable fragment scFv16
  • Ligand: 3-[(1S,2S)-1-(5-[(4S)-2,2-dimethyloxan-4-yl]-2-{(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carbonyl}-1H-indol-1-yl)-2-methylcyclopropyl]-1,2,4-oxadiazol-5(4H)-one
KeywordsClass B GPCR / glucagon-like peptide-1 receptor / G protein nucleotide exchange factor. / MEMBRANE PROTEIN
Function / homology
Function and homology information


glucagon-like peptide 1 receptor activity / glucagon receptor activity / sensory perception of chemical stimulus / hormone secretion / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / positive regulation of blood pressure / post-translational protein targeting to membrane, translocation / beta-2 adrenergic receptor binding / regulation of heart contraction ...glucagon-like peptide 1 receptor activity / glucagon receptor activity / sensory perception of chemical stimulus / hormone secretion / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / positive regulation of blood pressure / post-translational protein targeting to membrane, translocation / beta-2 adrenergic receptor binding / regulation of heart contraction / response to psychosocial stress / PKA activation in glucagon signalling / peptide hormone binding / developmental growth / D1 dopamine receptor binding / Hedgehog 'off' state / activation of adenylate cyclase activity / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / cAMP-mediated signaling / negative regulation of blood pressure / adenylate cyclase activator activity / bone development / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / transmembrane signaling receptor activity / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / learning or memory / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / apical plasma membrane / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
GPCR, family 2, glucagon-like peptide-1 receptor / : / GPCR, family 2, glucagon-like peptide-1/glucagon receptor / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily ...GPCR, family 2, glucagon-like peptide-1 receptor / : / GPCR, family 2, glucagon-like peptide-1/glucagon receptor / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Glucagon-like peptide 1 receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha / Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsSun B / Kobilka BK
CitationJournal: Proc Natl Acad Sci U S A / Year: 2020
Title: Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.
Authors: Takahiro Kawai / Bingfa Sun / Hitoshi Yoshino / Dan Feng / Yoshiyuki Suzuki / Masanori Fukazawa / Shunsuke Nagao / David B Wainscott / Aaron D Showalter / Brian A Droz / Tong Sun Kobilka / ...Authors: Takahiro Kawai / Bingfa Sun / Hitoshi Yoshino / Dan Feng / Yoshiyuki Suzuki / Masanori Fukazawa / Shunsuke Nagao / David B Wainscott / Aaron D Showalter / Brian A Droz / Tong Sun Kobilka / Matthew P Coghlan / Francis S Willard / Yoshiki Kawabe / Brian K Kobilka / Kyle W Sloop /
Abstract: Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved ...Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. We report the discovery and mechanism of action of LY3502970 (OWL833), a nonpeptide GLP-1R agonist. LY3502970 is a partial agonist, biased toward G protein activation over β-arrestin recruitment at the GLP-1R. The molecule is highly potent and selective against other class B G protein-coupled receptors (GPCRs) with a pharmacokinetic profile favorable for oral administration. A high-resolution structure of LY3502970 in complex with active-state GLP-1R revealed a unique binding pocket in the upper helical bundle where the compound is bound by the extracellular domain (ECD), extracellular loop 2, and transmembrane helices 1, 2, 3, and 7. This mechanism creates a distinct receptor conformation that may explain the partial agonism and biased signaling of the compound. Further, interaction between LY3502970 and the primate-specific Trp33 of the ECD informs species selective activity for the molecule. In efficacy studies, oral administration of LY3502970 resulted in glucose lowering in humanized GLP-1R transgenic mice and insulinotropic and hypophagic effects in nonhuman primates, demonstrating an effect size in both models comparable to injectable exenatide. Together, this work determined the molecular basis for the activity of an oral agent being developed for the treatment of type 2 diabetes mellitus, offering insights into the activation of class B GPCRs by nonpeptide ligands.
History
DepositionJul 7, 2020-
Header (metadata) releaseNov 18, 2020-
Map releaseNov 18, 2020-
UpdateOct 9, 2024-
Current statusOct 9, 2024Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.02
  • Imaged by UCSF Chimera
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  • Surface view colored by height
  • Surface level: 0.02
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  • Surface view with fitted model
  • Atomic models: PDB-6xox
  • Surface level: 0.02
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_22283.png

Downloads & links

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Map

FileDownload / File: emd_22283.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.04 Å/pix.
x 240 pix.
= 249.6 Å		1.04 Å/pix.
x 240 pix.
= 249.6 Å		1.04 Å/pix.
x 240 pix.
= 249.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.04 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.02 / Movie #1: 0.02
Minimum - Maximum-0.047277283 - 0.09817849
Average (Standard dev.)-0.000002493219 (±0.003445486)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 249.59999 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.041.041.04
M x/y/z240240240
origin x/y/z0.0000.0000.000
length x/y/z249.600249.600249.600
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ256256256
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS240240240
D min/max/mean-0.0470.098-0.000

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Supplemental data

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Sample components

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Entire : Cryo-EM structure of the Glucagon-like peptide-1 receptor in comp...

EntireName: Cryo-EM structure of the Glucagon-like peptide-1 receptor in complex with G protein and a non-peptide agonist LY3502970
Components
  • Complex: Cryo-EM structure of the Glucagon-like peptide-1 receptor in complex with G protein and a non-peptide agonist LY3502970
    • Complex: Glucagon-like peptide 1 receptor
      • Protein or peptide: Glucagon-like peptide 1 receptor
    • Complex: Trimeric stimulatory G protein
      • Protein or peptide: Alpha subunit of Gs with N-terminus swapped with equivalent residues in Gi,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Complex: Nanobody 35
      • Protein or peptide: Nanobody 35
    • Complex: Single-chain variable fragment 16
      • Protein or peptide: single-chain variable fragment scFv16
  • Ligand: 3-[(1S,2S)-1-(5-[(4S)-2,2-dimethyloxan-4-yl]-2-{(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carbonyl}-1H-indol-1-yl)-2-methylcyclopropyl]-1,2,4-oxadiazol-5(4H)-one

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Supramolecule #1: Cryo-EM structure of the Glucagon-like peptide-1 receptor in comp...

SupramoleculeName: Cryo-EM structure of the Glucagon-like peptide-1 receptor in complex with G protein and a non-peptide agonist LY3502970
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Molecular weightTheoretical: 150 KDa

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Supramolecule #2: Glucagon-like peptide 1 receptor

SupramoleculeName: Glucagon-like peptide 1 receptor / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #6
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: Trimeric stimulatory G protein

SupramoleculeName: Trimeric stimulatory G protein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1-#2, #4
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #4: Nanobody 35

SupramoleculeName: Nanobody 35 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #5
Source (natural)Organism: Lama glama (llama)

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Supramolecule #5: Single-chain variable fragment 16

SupramoleculeName: Single-chain variable fragment 16 / type: complex / ID: 5 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Mus musculus (house mouse)

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Macromolecule #1: Alpha subunit of Gs with N-terminus swapped with equivalent resid...

MacromoleculeName: Alpha subunit of Gs with N-terminus swapped with equivalent residues in Gi,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.385246 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG AGESGKSTIV KQMRILHVNG FNGDSEKATK VQDIKNNLKE AIETIVAAM SNLVPPVELA NPENQFRVDY ILSVMNVPDF DFPPEFYEHA KALWEDEGVR ACYERSNEYQ LIDCAQYFLD K IDVIKQAD ...String:
MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG AGESGKSTIV KQMRILHVNG FNGDSEKATK VQDIKNNLKE AIETIVAAM SNLVPPVELA NPENQFRVDY ILSVMNVPDF DFPPEFYEHA KALWEDEGVR ACYERSNEYQ LIDCAQYFLD K IDVIKQAD YVPSDQDLLR CRVLTSGIFE TKFQVDKVNF HMFDVGGQRD ERRKWIQCFN DVTAIIFVVA SSSYNMVIRE DN QTNRLQE ALNLFKSIWN NRWLRTISVI LFLNKQDLLA EKVLAGKSKI EDYFPEFARY TTPEDATPEP GEDPRVTRAK YFI RDEFLR ISTASGDGRH YCYPHFTCAV DTENIRRVFN DCRDIIQRMH LRQYELL

UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha, Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas

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Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 38.534062 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...String:
MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

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Macromolecule #3: single-chain variable fragment scFv16

MacromoleculeName: single-chain variable fragment scFv16 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 27.784896 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String:
DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH

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Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.861143 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

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Macromolecule #5: Nanobody 35

MacromoleculeName: Nanobody 35 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 17.352498 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A

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Macromolecule #6: Glucagon-like peptide 1 receptor

MacromoleculeName: Glucagon-like peptide 1 receptor / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 51.233109 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MKTIIALSYI FCLVFADYKD DDDAAAGGSG GSLEVLFQGP GGSGGSRPQG ATVSLWETVQ KWREYRRQCQ RSLTEDPPPA TDLFCNRTF DEYACWPDGE PGSFVNVSCP WYLPWASSVP QGHVYRFCTA EGLWLQKDNS SLPWRDLSEC EESKRGERSS P EEQLLFLY ...String:
MKTIIALSYI FCLVFADYKD DDDAAAGGSG GSLEVLFQGP GGSGGSRPQG ATVSLWETVQ KWREYRRQCQ RSLTEDPPPA TDLFCNRTF DEYACWPDGE PGSFVNVSCP WYLPWASSVP QGHVYRFCTA EGLWLQKDNS SLPWRDLSEC EESKRGERSS P EEQLLFLY IIYTVGYALS FSALVIASAI LLGFRHLHCT RNYIHLNLFA SFILRALSVF IKDAALKWMY STAAQQHQWD GL LSYQDSL SCRLVFLLMQ YCVAANYYWL LVEGVYLYTL LAFSVFSEQW IFRLYVSIGW GVPLLFVVPW GIVKYLYEDE GCW TRNSNM NYWLIIRLPI LFAIGVNFLI FVRVICIVVS KLKANLMCKT DIKCRLAKST LTLIPLLGTH EVIFAFVMDE HARG TLRFI KLFTELSFTS FQGLMVAILY CFVNNEVQLE FRKSWERWRL

UniProtKB: Glucagon-like peptide 1 receptor

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Macromolecule #7: 3-[(1S,2S)-1-(5-[(4S)-2,2-dimethyloxan-4-yl]-2-{(4S)-2-(4-fluoro-...

MacromoleculeName: 3-[(1S,2S)-1-(5-[(4S)-2,2-dimethyloxan-4-yl]-2-{(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-4-methyl-2,4,6,7-tetrahydro-5H- ...Name: 3-[(1S,2S)-1-(5-[(4S)-2,2-dimethyloxan-4-yl]-2-{(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carbonyl}-1H-indol-1-yl)-2-methylcyclopropyl]-1,2,4-oxadiazol-5(4H)-one
type: ligand / ID: 7 / Number of copies: 1 / Formula: V6G
Molecular weightTheoretical: 882.956 Da
Chemical component information

ChemComp-V6G:
3-[(1S,2S)-1-(5-[(4S)-2,2-dimethyloxan-4-yl]-2-{(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-4-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carbonyl}-1H-indol-1-yl)-2-methylcyclopropyl]-1,2,4-oxadiazol-5(4H)-one

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration10 mg/mL
BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 10.8 sec. / Average electron dose: 81.56 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 1598390
Startup modelType of model: EMDB MAP
EMDB ID:

8653

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 583053
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

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Atomic model buiding 1

Initial modelPDB ID:

5vai


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementProtocol: FLEXIBLE FIT / Overall B value: 72.5
Output model

PDB-6xox:
cryo-EM of human GLP-1R bound to non-peptide agonist LY3502970

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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

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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

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