Evidence map›Paper›PMID 27453555›Full record

ArticleThe Journal of biological chemistry2016

Key Residues for Catalytic Function and Metal Coordination in a Carotenoid Cleavage Dioxygenase.

Xuewu Sui, Jianye Zhang, Marcin Golczak, Krzysztof Palczewski, Philip D Kiser

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Mechanism of Lutein tobioRxiv : the preprint server for biology · 2025
    Article
  2. Article
  3. Article
  4. Carotenoid Cleavage Dioxygenase GeneInternational journal of molecular sciences · 2024
    Article
  5. Article
  6. Retinal pigment epithelium 65 kDa protein (RPE65): An update.Progress in retinal and eye research · 2022
    Review
  7. Article
  8. GmCCD4 controls carotenoid content in soybeans.Plant biotechnology journal · 2021
    Article
  9. Review
  10. Assessing the Role ofFrontiers in nutrition · 2021
    Article
  11. Structural and mechanistic aspects of carotenoid cleavage dioxygenases (CCDs).Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020
    Review
  12. 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
  13. Crocetin Overproduction in EngineeredFrontiers in bioengineering and biotechnology · 2020
    Article
  14. Article
  15. Preparation and characterization of metal-substituted carotenoid cleavage oxygenases.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018
    Article
  16. Resveratrol as a Growth Substrate for Bacteria from the Rhizosphere.Applied and environmental microbiology · 2018
    Article
  17. Article
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

5 authors at 1 institution in 1 country.

Xuewu SuiFrom the Department of Pharmacology, School of Medicine, Case Western Reserve University and.
Jianye ZhangFrom the Department of Pharmacology, School of Medicine, Case Western Reserve University and.
Marcin GolczakFrom the Department of Pharmacology, School of Medicine, Case Western Reserve University and.
Krzysztof PalczewskiFrom the Department of Pharmacology, School of Medicine, Case Western Reserve University and kxp65@case.edu.ORCID 0000-0002-0788-545X
Philip D KiserFrom the Department of Pharmacology, School of Medicine, Case Western Reserve University and Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106 pdk7@case.edu.ORCID 0000-0003-1184-9539
Case Western Reserve University · US

Funding

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
Carotinoids in VisionR01EY020551 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI VON LINTIG, JOHANNES FRIEDRICH · 2011 to 2024
$4.8M
Regulation of vitamin A metabolism in the eyeR01EY023948 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI GOLCZAK, MARCIN BERNARD · 2014 to 2023
$3.8M
Studies on visual cycles and their relevance to age-related macular degenerationIK2BX002683 · VA · VETERANS HEALTH ADMINISTRATION · PI KISER, PHILIP DAVID · 2015 to 2019
–
BLRD VA IK2 BX002683NEI NIH HHS R01 EY009339NEI NIH HHS R01 EY020551NEI NIH HHS R01 EY023948NIGMS NIH HHS P41 GM103403
6 · The paper itself

Abstract

Carotenoid cleavage dioxygenases (CCDs) are non-heme iron-containing enzymes found in all domains of life that generate biologically important apocarotenoids. Prior studies have revealed a critical role for a conserved 4-His motif in forming the CCD iron center. By contrast, the roles of other active site residues in catalytic function, including maintenance of the stringent regio- and stereo-selective cleavage activity, typically exhibited by these enzymes have not been thoroughly investigated. Here, we examined the functional and structural importance of active site residues in an apocarotenoid-cleaving oxygenase (ACO) from Synechocystis Most active site substitutions variably lowered maximal catalytic activity without markedly affecting the Km value for the all-trans-8'-apocarotenol substrate. Native C15-C15' cleavage activity was retained in all ACO variants examined suggesting that multiple active site residues contribute to the enzyme's regioselectivity. Crystallographic analysis of a nearly inactive W149A-substituted ACO revealed marked disruption of the active site structure, including loss of iron coordination by His-238 apparently from an altered conformation of the conserved second sphere Glu-150 residue. Gln- and Asp-150-substituted versions of ACO further confirmed the structural/functional requirement for a Glu side chain at this position, which is homologous to Glu-148 in RPE65, a site in which substitution to Asp has been associated with loss of enzymatic function in Leber congenital amaurosis. The novel links shown here between ACO active site structure and catalytic activity could be broadly applicable to other CCD members and provide insights into the molecular pathogenesis of vision loss associated with an RPE65 point mutation.

Indexed as

Amino Acid SubstitutionBacterial ProteinsCatalysisCatalytic DomainDioxygenasesIronMutation, MissenseSynechocystisBacterial ProteinsDioxygenasesIronenzyme mutationLeber congenital amaurosismetalloenzymenon-heme ironregioselectivityretinalrhodopsinRPE65site-directed mutagenesisx-ray crystallography

Identifiers

PMID27453555
PMCPMC5016679
OpenAlexW2495702130

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.