4O9R | pdb_00004o9r

Human Smoothened Receptor structure in complex with cyclopamine

PDB DOI:&nbsphttps://doi.org/10.2210/pdb4O9R/pdb

Classification:&nbspSIGNALING PROTEIN
Organism(s):&nbspHomo sapiens, Escherichia coli
Expression System:&nbspSpodoptera frugiperda
Mutation(s):&nbspYes&nbsp
Membrane Protein:&nbspYes&nbsp&nbspPDBTMMemProtMDmpstruc

Deposited:&nbsp2014-01-02&nbspReleased:&nbsp2014-03-05&nbsp
Deposition Author(s):&nbspWang, C., Weierstall, U., James, D., White, T.A., Wang, D., Liu, W., Spence, J.C.H., Doak, R.B., Nelson, G., Fromme, P., Fromme, R., Grotjohann, I., Kupitz, C., Zatsepin, N.A., Liu, H., Basu, S., Wacker, D., Han, G.W., Katritch, V., Boutet, S., Messerschmidt, M., Willams, G.J., Koglin, J.E., Seibert, M.M., Klinker, M., Gati, C., Shoeman, R.L., Barty, A., Chapman, H.N., Kirian, R.A., Beyerlein, K.R., Stevens, R.C., Li, D., Shah, S.T.A., Howe, N., Caffrey, M., Cherezov, V., GPCR Network (GPCR)

Experimental Data Snapshot

Method:&nbspX-RAY DIFFRACTION
Resolution:&nbsp3.20 Å
R-Value Free:&nbsp
0.278 (Depositor), 0.280 (DCC)&nbsp
R-Value Work:&nbsp
0.232 (Depositor), 0.240 (DCC)&nbsp
R-Value Observed:&nbsp
0.234&nbsp(Depositor)&nbsp

Starting Models: experimental
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wwPDB Validation&nbsp 3D Report&nbspFull Report

Ligand Structure Quality Assessment&nbsp

This is version 1.5 of the entry. See complete&nbsphistory.&nbsp

Literature

Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography.

Weierstall, U.,&nbspJames, D.,&nbspWang, C.,&nbspWhite, T.A.,&nbspWang, D.,&nbspLiu, W.,&nbspSpence, J.C.,&nbspBruce Doak, R.,&nbspNelson, G.,&nbspFromme, P.,&nbspFromme, R.,&nbspGrotjohann, I.,&nbspKupitz, C.,&nbspZatsepin, N.A.,&nbspLiu, H.,&nbspBasu, S.,&nbspWacker, D.,&nbspHan, G.W.,&nbspKatritch, V.,&nbspBoutet, S.,&nbspMesserschmidt, M.,&nbspWilliams, G.J.,&nbspKoglin, J.E.,&nbspMarvin Seibert, M.,&nbspKlinker, M.,&nbspGati, C.,&nbspShoeman, R.L.,&nbspBarty, A.,&nbspChapman, H.N.,&nbspKirian, R.A.,&nbspBeyerlein, K.R.,&nbspStevens, R.C.,&nbspLi, D.,&nbspShah, S.T.,&nbspHowe, N.,&nbspCaffrey, M.,&nbspCherezov, V.

(2014) Nat Commun&nbsp5: 3309-3309

PubMed:&nbsp24525480&nbspSearch on PubMedSearch on PubMed Central
DOI:&nbsphttps://doi.org/10.1038/ncomms4309
Primary Citation of Related Structures: &nbsp
4O9R

PubMed Abstract:&nbsp
Lipidic cubic phase (LCP) crystallization has proven successful for high-resolution structure determination of challenging membrane proteins. Here we present a technique for extruding gel-like LCP with embedded membrane protein microcrystals, providing a continuously renewed source of material for serial femtosecond crystallography. Data collected from sub-10-μm-sized crystals produced with less than 0.5 mg of purified protein yield structural insights regarding cyclopamine binding to the Smoothened receptor.

Organizational Affiliation

Department of Physics, Arizona State University, Tempe, Arizona 85287, USA.

Macromolecule Content

Total Structure Weight: 52.81 kDa&nbsp
Atom Count: 3,419&nbsp
Modelled Residue Count: 441&nbsp
Deposited Residue Count: 468&nbsp
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Smoothened homolog/Soluble cytochrome b562 chimeric protein	A	468	Homo sapiens,&nbspEscherichia coli	Mutation(s): 3&nbsp Membrane Entity:&nbspYes&nbsp
UniProt & NIH Common Fund Data Resources
Find proteins for&nbspP0ABE7&nbsp(Escherichia coli) Explore&nbspP0ABE7&nbsp Go to UniProtKB: &nbspP0ABE7
Find proteins for&nbspQ99835&nbsp(Homo sapiens) Explore&nbspQ99835&nbsp Go to UniProtKB: &nbspQ99835
PHAROS: &nbspQ99835 GTEx: &nbspENSG00000128602&nbsp
Entity Groups &nbsp
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Groups	P0ABE7Q99835
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands&nbsp1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
CY8 Query on CY8 Download Ideal Coordinates CCD File&nbsp SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	Cyclopamine C₂₇ H₄₁ N O₂ QASFUMOKHFSJGL-LAFRSMQTSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations&nbsp
ID	Source	Binding Affinity
CY8	BindingDB:&nbsp 4O9R	Ki:&nbsp12.7&nbsp(nM) from 1 assay(s)
		Kd:&nbsp12.4&nbsp(nM) from 1 assay(s)
		IC50:&nbspmin: 64, max: 1900&nbsp(nM) from 7 assay(s)

Experimental Data & Validation

Experimental Data

Method:&nbspX-RAY DIFFRACTION
Resolution:&nbsp3.20 Å
R-Value Free:&nbsp 0.278 (Depositor), 0.280 (DCC)&nbsp
R-Value Work:&nbsp 0.232 (Depositor), 0.240 (DCC)&nbsp
R-Value Observed:&nbsp0.234&nbsp(Depositor)&nbsp

Diffraction Data:&nbsphttps://doi.org/10.11577/1255979

Space Group:&nbspP 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 40.5	α = 90
b = 157.3	β = 97
c = 52.4	γ = 90

Software Package:

Software Name	Purpose
PHASER	phasing
PHENIX	refinement
CrystFEL	data reduction
CrystFEL	data scaling

Structure Validation

View&nbspFull Validation Report

Ligand Structure Quality Assessment&nbsp

Entry History&nbsp

Deposition Data

Released Date:&nbsp2014-03-05&nbsp

Deposition Author(s):&nbsp

Revision History (Full details and data files)

Version 1.0: 2014-03-05
Type: Initial release
Version 1.1: 2017-08-02
Changes: Refinement description, Source and taxonomy
Version 1.2: 2018-02-14
Changes: Data collection
Version 1.3: 2023-08-16
Changes: Data collection, Database references, Derived calculations
Version 1.4: 2023-09-20
Changes: Refinement description
Version 1.5: 2024-10-16
Changes: Structure summary