Evidence map›Paper›PMID 23012475›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Structure of RPE65 isomerase in a lipidic matrix reveals roles for phospholipids and iron in catalysis.

Philip D Kiser, Erik R Farquhar, Wuxian Shi, Xuewu Sui, Mark R Chance, Krzysztof Palczewski

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

48 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Mechanism of Lutein tobioRxiv : the preprint server for biology · 2025
    Article
  3. Article
  4. A novelFrontiers in medicine · 2024
    Article
  5. Article
  6. Article
  7. The Amphipathic Helix in Visual Cycle Proteins: A Review.Advances in experimental medicine and biology · 2023
    Review
  8. Predicting potentially pathogenic effects ofJournal of enzyme inhibition and medicinal chemistry · 2022
    Article
  9. Retinal pigment epithelium 65 kDa protein (RPE65): An update.Progress in retinal and eye research · 2022
    Review
  10. Article
  11. GmCCD4 controls carotenoid content in soybeans.Plant biotechnology journal · 2021
    Article
  12. Review
  13. Review
  14. Review
  15. Evolutionary aspects and enzymology of metazoan carotenoid cleavage oxygenases.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020
    Review
  16. Structural and mechanistic aspects of carotenoid cleavage dioxygenases (CCDs).Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020
    Review
  17. Shedding new light on the generation of the visual chromophore.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Review
  18. Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  19. Article
  20. RPE65 Palmitoylation: A Tale of Lipid Posttranslational Modification.Advances in experimental medicine and biology · 2019
    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

6 authors at 1 institution in 1 country.

Philip D KiserDepartment of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. pdk7@case.edu
Erik R Farquhar
Wuxian Shi
Xuewu Sui
Mark R Chance
Krzysztof Palczewski
Case Western Reserve University · US

Funding

Y-FAMILY POLYMERASES AND CO-FACTORS IN TRANSLESION REPLICATIONP41RR015301 · NCRR · CORNELL UNIVERSITY ITHACA · PI RAO, ANJANA · 2001 to 2011
$28.2M
TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI CARLOS S SUBAUSTE · 1997 to 2026
$17.7M
STRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Case Center for Synchrotron BiosciencesP30EB009998 · NIBIB · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2009 to 2018
$8.4M
Carotinoids in VisionR01EY020551 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI VON LINTIG, JOHANNES FRIEDRICH · 2011 to 2024
$4.8M
NCRR NIH HHS 5P41RR015301-10NCRR NIH HHS P41 RR015301NEI NIH HHS EY009339NEI NIH HHS EY020551NEI NIH HHS P30 EY011373NEI NIH HHS P30-EY011373NEI NIH HHS R01 EY009339NEI NIH HHS R01 EY020551NIBIB NIH HHS P30 EB009998NIBIB NIH HHS P30-EB-009998NIGMS NIH HHS 8P41GM103403-10NIGMS NIH HHS P41 GM103403
6 · The paper itself

Abstract

RPE65 is a key metalloenzyme responsible for maintaining visual function in vertebrates. Despite extensive research on this membrane-bound retinoid isomerase, fundamental questions regarding its enzymology remain unanswered. Here, we report the crystal structure of RPE65 in a membrane-like environment. These crystals, obtained from enzymatically active, nondelipidated protein, displayed an unusual packing arrangement wherein RPE65 is embedded in a lipid-detergent sheet. Structural differences between delipidated and nondelipidated RPE65 uncovered key residues involved in substrate uptake and processing. Complementary iron K-edge X-ray absorption spectroscopy data established that RPE65 as isolated contained a divalent iron center and demonstrated the presence of a tightly bound ligand consistent with a coordinated carboxylate group. These results support the hypothesis that the Lewis acidity of iron could be used to promote ester dissociation and generation of a carbocation intermediate required for retinoid isomerization.

Indexed as

Amino Acid SequenceAnimalsBinding SitesCatalysisCattlecis-trans-IsomerasesCrystallography, X-RayIronLipidsMicrosomesModels, MolecularMolecular Sequence DataPhospholipidsProtein ConformationProtein Structure, TertiaryRetinal Pigment Epitheliumcis-trans-IsomerasesIronLipidsPhospholipids

Identifiers

PMID23012475
PMCPMC3478654
OpenAlexW2090239623

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.