Evidence map›Paper›PMID 26342082›Full record

ArticleThe Journal of biological chemistry2015

Sph3 Is a Glycoside Hydrolase Required for the Biosynthesis of Galactosaminogalactan in Aspergillus fumigatus.

Natalie C Bamford, Brendan D Snarr, Fabrice N Gravelat, Dustin J Little, Mark J Lee, Caitlin A Zacharias, Josée C Chabot, Alexander M Geller, Stefanie D Baptista, Perrin Baker and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
7.8field-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

51 citing papers in PubMed, 99 citations in OpenAlex.

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  13. UnderstandingCell surface (Amsterdam, Netherlands) · 2023
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  17. Identification of Compounds PreventingInternational journal of molecular sciences · 2023
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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

13 authors at 4 institutions in 2 countries.

Natalie C BamfordFrom the Program in Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Brendan D Snarrthe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and.
Fabrice N Gravelatthe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and.
Dustin J LittleFrom the Program in Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Mark J Leethe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and.
Caitlin A Zachariasthe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and.
Josée C Chabotthe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and.
Alexander M Gellerthe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and.
Stefanie D Baptistathe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and.
Perrin BakerFrom the Program in Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
Howard Robinsonthe Photon Sciences Division, Brookhaven National Laboratory, Upton, New York 11973-5000.
P Lynne HowellFrom the Program in Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada, howell@sickkids.ca.
Donald C Sheppardthe Departments of Microbiology and Immunology and Medicine, McGill University, Montréal, Québec H4A 3J1, Canada, and don.sheppard@mcgill.ca.
McGill University · CAHospital for Sick Children · CABrookhaven National Laboratory · USUniversity of Toronto · CA

Funding

X-RAY STRUCTURE OF RIFM PROTEIN FROM THE BIOSYNTHESIS PATHWAY OF THE ANSAMYCIN AP41RR012408 · NCRR · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI ORVILLE, ALLEN M · 1998 to 2011
$32.2M
Macromolecular Crystallography at the National Synchrotron Light SourceP41GM103473 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI SWEET, ROBERT M · 2012 to 2013
$4.9M
Canadian Institutes of Health Research 123306Canadian Institutes of Health Research 81361NCRR NIH HHS P41 RR012408NIGMS NIH HHS P41 GM103473
6 · The paper itself

Abstract

Aspergillus fumigatus is the most virulent species within the Aspergillus genus and causes invasive infections with high mortality rates. The exopolysaccharide galactosaminogalactan (GAG) contributes to the virulence of A. fumigatus. A co-regulated five-gene cluster has been identified and proposed to encode the proteins required for GAG biosynthesis. One of these genes, sph3, is predicted to encode a protein belonging to the spherulin 4 family, a protein family with no known function. Construction of an sph3-deficient mutant demonstrated that the gene is necessary for GAG production. To determine the role of Sph3 in GAG biosynthesis, we determined the structure of Aspergillus clavatus Sph3 to 1.25 Å. The structure revealed a (β/α)8 fold, with similarities to glycoside hydrolase families 18, 27, and 84. Recombinant Sph3 displayed hydrolytic activity against both purified and cell wall-associated GAG. Structural and sequence alignments identified three conserved acidic residues, Asp-166, Glu-167, and Glu-222, that are located within the putative active site groove. In vitro and in vivo mutagenesis analysis demonstrated that all three residues are important for activity. Variants of Asp-166 yielded the greatest decrease in activity suggesting a role in catalysis. This work shows that Sph3 is a glycoside hydrolase essential for GAG production and defines a new glycoside hydrolase family, GH135.

Indexed as

Amino Acid SequenceAspergillus fumigatusCatalysisCatalytic DomainCell WallCoccidioidinConserved SequenceCrystallography, X-RayFungal ProteinsGlycoside HydrolasesHydrolysisMolecular Sequence DataMutationPolysaccharidesProtein ConformationSequence AlignmentCoccidioidinFungal ProteinsgalactosaminogalactanGlycoside HydrolasesPolysaccharidesspherulinAspergillusbiofilmcarbohydrate biosynthesiscrystal structuregalactosaminogalactanglycoside hydrolasein vivo imagingmutagenesis in vitropolysaccharideSph3

Identifiers

PMID26342082
PMCPMC4645995
OpenAlexW1882026650

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.