Evidence map›Paper›PMID 26190575›Full record

ArticleStructure (London, England : 1993)2015

Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral Ceramidase.

Michael V Airola, William J Allen, Michael J Pulkoski-Gross, Lina M Obeid, Robert C Rizzo, Yusuf A Hannun

Open access · bronzeAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
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  13. Targeted proteomic response to coffee consumption.European journal of nutrition · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Michael V AirolaDepartment of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Medicine, Stony Brook Cancer Center, Stony Brook, NY 11794, USA.
William J AllenDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Michael J Pulkoski-GrossDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
Lina M ObeidDepartment of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Medicine, Stony Brook Cancer Center, Stony Brook, NY 11794, USA; Department of Medicine, Northport Veterans Affairs Medical Center, Northport, NY 11768, USA.
Robert C RizzoDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
Yusuf A HannunDepartment of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Medicine, Stony Brook Cancer Center, Stony Brook, NY 11794, USA. Electronic address: yusuf.hannun@stonybrookmedicine.edu.
Stony Brook Medicine · USStony Brook University · US

Funding

Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Daniel Canals · 2003 to 2026
$30.8M
Training Program in Pharmacological SciencesT32GM007518 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI GARCIA-DIAZ, MIGUEL · 1985 to 2021
$5.4M
Sphingomyelin Turnover and Cellular RegulationR37GM043825 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2007 to 2015
$3.7M
Role and Regulation of Ceramide Synthases in ApoptosisR01GM097741 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI LUBERTO, CHIARA · 2011 to 2019
$3.5M
Neutral Ceramidase in Colon CancerR01CA172517 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2013 to 2016
$1.3M
Regulation of Neutral Sphingomyelinase 2 by Inter-Domain InteractionsF32GM100679 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI AIROLA, MICHAEL VIRGIL · 2012 to 2014
$102k
Regulation and Role of Ceramidase in InflammationI01BX000156 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI OBEID, LINA M · 2009 to 2017
–
BLRD VA I01 BX000156NCI NIH HHS P01 CA097132NCI NIH HHS R01 CA172517NCI NIH HHS R01CA172517NIGMS NIH HHS F32 GM100679NIGMS NIH HHS F32GM100679NIGMS NIH HHS R01 GM097741NIGMS NIH HHS R01GM097741NIGMS NIH HHS R37 GM043825NIGMS NIH HHS T32 GM007518NIGMS NIH HHS T32GM007518
6 · The paper itself

Abstract

Neutral ceramidase (nCDase) catalyzes conversion of the apoptosis-associated lipid ceramide to sphingosine, the precursor for the proliferative factor sphingosine-1-phosphate. As an enzyme regulating the balance of ceramide and sphingosine-1-phosphate, nCDase is emerging as a therapeutic target for cancer. Here, we present the 2.6-Å crystal structure of human nCDase in complex with phosphate that reveals a striking, 20-Å deep, hydrophobic active site pocket stabilized by a eukaryotic-specific subdomain not present in bacterial ceramidases. Utilizing flexible ligand docking, we predict a likely binding mode for ceramide that superimposes closely with the crystallographically observed transition state analog phosphate. Our results suggest that nCDase uses a new catalytic strategy for Zn(2+)-dependent amidases, and generates ceramide specificity by sterically excluding sphingolipids with bulky headgroups and specifically recognizing the small hydroxyl head group of ceramide. Together, these data provide a foundation to aid drug development and establish common themes for how proteins recognize the bioactive lipid ceramide.

Indexed as

Amino Acid SequenceAnimalsCatalytic DomainCeramidesCrystallography, X-RayEscherichia coliHumansHydrolysisHydrophobic and Hydrophilic InteractionsKineticsLigandsLysophospholipidsMolecular Docking SimulationMolecular Sequence DataNeutral CeramidaseProtein BindingASAH2 protein, humanCeramidesLigandsLysophospholipidsNeutral CeramidaseRecombinant ProteinsSphingosinesphingosine 1-phosphate

Identifiers

PMID26190575
PMCPMC4830088
OpenAlexW1880491872

What OpenQuestion holds

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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.