Evidence map›Paper›PMID 26851242›Full record

ReviewDrug metabolism and disposition: the biological fate of chemicals2016

The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function.

Emily E Scott, C Roland Wolf, Michal Otyepka, Sara C Humphreys, James R Reed, Colin J Henderson, Lesley A McLaughlin, Markéta Paloncýová, Veronika Navrátilová, Karel Berka and 9 more

Open access · bronzeAbstract readReview
In one paragraph

Review in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
8.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
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  13. CytochromeThe Plant cell · 2019
    Article
  14. Ligand Access Channels in Cytochrome P450 Enzymes: A Review.International journal of molecular sciences · 2018
    Review
  15. Article
  16. Article
  17. Article
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 3 countries.

Emily E ScottDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
C Roland WolfDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Michal OtyepkaDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Sara C HumphreysDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
James R ReedDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Colin J HendersonDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Lesley A McLaughlinDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Markéta PaloncýováDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Veronika NavrátilováDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Karel BerkaDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Pavel AnzenbacherDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Upendra P DahalDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Carlo BarnabaDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
James A BrozikDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Jeffrey P JonesDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
D Fernando EstradaDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Jennifer S LaurenceDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Ji Won ParkDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.).
Wayne L BackesDepartments of Medicinal Chemistry and Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas (D.F.E, J.S.L., E.E.S.); Division of Cancer Research, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, United Kingdom (C.R.W., C.J.H., L.A.M.); Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science (M.O., M.P., V.N., K.B.) and Department of Pharmacology, Faculty of Medicine and Dentistry (P.A.), Palacký University, Olomouc, Czech Republic; Department of Chemistry, Washington State University, Pullman, Washington (S.C.H., U.P.D., C.B., J.A.B., J.P.J.); and Department of Pharmacology and Experimental Therapeutics, and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana (J.R.R., J.W.P., W.L.B.) wbacke@lsuhsc.edu.
Ninewells Hospital · GBLouisiana State University Health Sciences Center New Orleans · USPalacký University Olomouc · CZRegional Centre of Advanced Technologies and Materials · CZUniversity of Dundee · GBWashington State University · US

Funding

Role of microbiota in increased influenza severity due to particulate matter exposureP42ES013648 · NIEHS · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI SPRUNGER, PHILLIP · 2009 to 2024
$27.6M
TOXICOLOGICAL SIGNIFICANCE OF ALKYLBENZENE METABOLISMR01ES004344 · NIEHS · LSU HEALTH SCIENCES CENTER · PI BACKES, WAYNE L · 1996 to 2013
$4.0M
Structural Basis of Cytochrome P450 Activity-Equipment SupplementR37GM076343 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT, EMILY E · 2015 to 2024
$3.7M
Improving prediction of drug interactions mediated by time-dependent inhibitorsR01GM114369 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI KORZEKWA, KENNETH RAY, NAGAR, SWATI · 2016 to 2023
$3.2M
Structural Basis of Cytochrome P450 ActivityR01GM076343 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI SCOTT, EMILY E · 2006 to 2014
$2.9M
P450-Base Drug Interactions with Low Spin DrugsR01GM110790 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 2013 to 2016
$1.7M
Structure and Function of Cytochrome P450 17A1R01GM102505 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AUBE, JEFFREY, SCOTT, EMILY E · 2012 to 2015
$1.2M
Application of solution NMR to (human) membrane cytochrome P450 17A1F32GM103069 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI ESTRADA, DAVID FERNANDO · 2012 to 2014
$102k
Cancer Research UK 10822Cancer Research UK 22357Cancer Research UK C4639/A10822NIEHS NIH HHS P42 ES013648NIEHS NIH HHS R01 ES004344NIGMS NIH HHS F32 GM103069NIGMS NIH HHS GM102505NIGMS NIH HHS GM110790NIGMS NIH HHS R01 GM076343NIGMS NIH HHS R01 GM102505NIGMS NIH HHS R01 GM110790NIGMS NIH HHS R01 GM114369NIGMS NIH HHS R37 GM076343
6 · The paper itself

Abstract

This symposium summary, sponsored by the ASPET, was held at Experimental Biology 2015 on March 29, 2015, in Boston, Massachusetts. The symposium focused on: 1) the interactions of cytochrome P450s (P450s) with their redox partners; and 2) the role of the lipid membrane in their orientation and stabilization. Two presentations discussed the interactions of P450s with NADPH-P450 reductase (CPR) and cytochrome b5. First, solution nuclear magnetic resonance was used to compare the protein interactions that facilitated either the hydroxylase or lyase activities of CYP17A1. The lyase interaction was stimulated by the presence of b5 and 17α-hydroxypregnenolone, whereas the hydroxylase reaction was predominant in the absence of b5. The role of b5 was also shown in vivo by selective hepatic knockout of b5 from mice expressing CYP3A4 and CYP2D6; the lack of b5 caused a decrease in the clearance of several substrates. The role of the membrane on P450 orientation was examined using computational methods, showing that the proximal region of the P450 molecule faced the aqueous phase. The distal region, containing the substrate-access channel, was associated with the membrane. The interaction of NADPH-P450 reductase (CPR) with the membrane was also described, showing the ability of CPR to "helicopter" above the membrane. Finally, the endoplasmic reticulum (ER) was shown to be heterogeneous, having ordered membrane regions containing cholesterol and more disordered regions. Interestingly, two closely related P450s, CYP1A1 and CYP1A2, resided in different regions of the ER. The structural characteristics of their localization were examined. These studies emphasize the importance of P450 protein organization to their function.

Indexed as

Research ReportAnimalsCell MembraneCytochrome P-450 Enzyme SystemEndoplasmic ReticulumHumansMicrosomes, LiverProtein Interaction Domains and MotifsProtein Structure, SecondaryCytochrome P-450 Enzyme System

Identifiers

PMID26851242
PMCPMC4810767
OpenAlexW2265327458

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.