Evidence map›Paper›PMID 26349049›Full record

ArticleScientific reports2015

The identification of an integral membrane, cytochrome c urate oxidase completes the catalytic repertoire of a therapeutic enzyme.

Nicola Doniselli, Enrico Monzeglio, Alessandro Dal Palù, Angelo Merli, Riccardo Percudani

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

10 citing papers in PubMed, 24 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Nicola DoniselliDepartment of Life Sciences, University of Parma, Italy.
Enrico MonzeglioDepartment of Life Sciences, University of Parma, Italy.
Alessandro Dal PalùDepartment of Mathematics &Computer Science, University of Parma, Italy.
Angelo MerliDepartment of Life Sciences, University of Parma, Italy.
Riccardo PercudaniDepartment of Life Sciences, University of Parma, Italy.
University of Parma · IT

Funding

Telethon GGP13149
6 · The paper itself

Abstract

In living organisms, the conversion of urate into allantoin requires three consecutive enzymes. The pathway was lost in hominid, predisposing humans to hyperuricemia and gout. Among other species, the genomic distribution of the two last enzymes of the pathway is wider than that of urate oxidase (Uox), suggesting the presence of unknown genes encoding Uox. Here we combine gene network analysis with association rule learning to identify the missing urate oxidase. In contrast with the known soluble Uox, the identified gene (puuD) encodes a membrane protein with a C-terminal cytochrome c. The 8-helix transmembrane domain corresponds to DUF989, a family without similarity to known proteins. Gene deletion in a PuuD-encoding organism (Agrobacterium fabrum) abolished urate degradation capacity; the phenotype was fully restored by complementation with a cytosolic Uox from zebrafish. Consistent with H2O2 production by zfUox, urate oxidation in the complemented strain caused a four-fold increase of catalase. No increase was observed in the wild-type, suggesting that urate oxidation by PuuD proceeds through cytochrome c-mediated electron transfer. These findings identify a missing link in purine catabolism, assign a biochemical activity to a domain of unknown function (DUF989), and complete the catalytic repertoire of an enzyme useful for human therapy.

Indexed as

Protein Interaction Domains and MotifsAgrobacteriumAmino Acid SequenceAmmoniaCatalaseCytochromes cGene DeletionGene ExpressionMembrane ProteinsMolecular Sequence DataOxidation-ReductionPhenotypeSequence AlignmentSolubilityUrate OxidaseUric AcidAmmoniaCatalaseCytochromes cMembrane ProteinsUrate OxidaseUric Acid

Identifiers

PMID26349049
PMCPMC4562309
OpenAlexW1618144532

What OpenQuestion holds

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Registered trials

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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.