Evidence map›Paper›PMID 23259842›Full record

ArticleBiochemistry2013

Structural and mechanistic studies of HpxO, a novel flavin adenine dinucleotide-dependent urate oxidase from Klebsiella pneumoniae.

Katherine A Hicks, Seán E O'Leary, Tadhg P Begley, Steven E Ealick

Abstract read
In one paragraph

Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

13 citing papers in PubMed, 48 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

4 authors at 2 institutions in 1 country.

Katherine A HicksDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Seán E O'Leary
Tadhg P Begley
Steven E Ealick
Cornell University · USTexas A&M University · US

Funding

Y-FAMILY POLYMERASES AND CO-FACTORS IN TRANSLESION REPLICATIONP41RR015301 · NCRR · CORNELL UNIVERSITY ITHACA · PI EISENBERG, DAVID · 2001 to 2011
$28.2M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Structural Biology of Purine and Pyrimidine Biosynthesis and MetabolismR01GM073220 · NIGMS · CORNELL UNIVERSITY ITHACA · PI EALICK, STEVEN E · 2005 to 2012
$2.4M
NCRR NIH HHS P41 RR015301NIGMS NIH HHS GM073220NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R01 GM073220
6 · The paper itself

Abstract

HpxO is a flavin-dependent urate oxidase that catalyzes the hydroxylation of uric acid to 5-hydroxyisourate and functions in a novel pathway for purine catabolism found in Klebsiella pneumoniae. We have determined the structures of HpxO with and without uric acid at 2.0 and 2.2 Å, respectively. We have also determined the structure of the R204Q variant at 2.0 Å resolution in the absence of uric acid. The variant structure is very similar to that of wild-type HpxO except for the conformation of Arg103, which interacts with FAD in the variant but not in the wild-type structure. Interestingly, the R204Q variant results in the uncoupling of nicotinamide adenine dinucleotide oxidation from uric acid hydroxylation. This suggests that Arg204 facilitates the deprotonation of uric acid, activating it for the oxygen transfer. On the basis of these data, a mechanism for this reaction consisting of a nucleophilic attack of the urate anion on the flavin hydroperoxide resulting in the formation of 5-hydroxyisourate is proposed.

Indexed as

Amino Acid SubstitutionBacterial ProteinsBiocatalysisCatalytic DomainCrystallography, X-RayFlavin-Adenine DinucleotideHydroxylationKineticsKlebsiella pneumoniaeLigandsModels, MolecularMolecular ConformationMutagenesis, Site-DirectedMutant ProteinsNADOxidation-Reduction5-hydroxyisourateBacterial ProteinsFlavin-Adenine DinucleotideLigandsMutant ProteinsNADRecombinant ProteinsUrate OxidaseUric Acid

Identifiers

PMID23259842
PMCPMC3552057
OpenAlexW2009204397

What OpenQuestion holds

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LicenceTDM
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.