Evidence map›Paper›PMID 24643289›Full record

ArticleNature communications2014

A highly efficient cocaine-detoxifying enzyme obtained by computational design.

Fang Zheng, Liu Xue, Shurong Hou, Junjun Liu, Max Zhan, Wenchao Yang, Chang-Guo Zhan

Open access · bronzeAbstract read
In one paragraph

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
9.8field-weighted citation impact, top 1% 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

39 citing papers in PubMed, 88 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

7 authors at 1 institution in 1 country.

Fang ZhengDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Liu XueDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Shurong HouDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Junjun LiuDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Max ZhanDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Wenchao YangDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
Chang-Guo ZhanDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
University of Kentucky · US

Funding

Long-lasting cocaine-metabolizing enzyme for cocaine addiction treatmentR01DA035552 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2013 to 2015
$3.4M
High-activity mutants of cocaine esterase for treatment of drug addictionR01DA025100 · NIDA · UNIVERSITY OF KENTUCKY · PI LANDRY, DONALD W, WOODS, JAMES H · 2008 to 2012
$2.5M
Redesign of Butyrylcholinesterase for Cocaine MetabolismR01DA013930 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2003 to 2010
$2.4M
Development of a Cocaine-Metabolizing Enzyme for Drug Overdose TreatmentR01DA032910 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2012 to 2015
$1.8M
NIDA NIH HHS R01 DA013930NIDA NIH HHS R01 DA025100NIDA NIH HHS R01 DA032910NIDA NIH HHS R01 DA035552
6 · The paper itself

Abstract

Compared with naturally occurring enzymes, computationally designed enzymes are usually much less efficient, with their catalytic activities being more than six orders of magnitude below the diffusion limit. Here we use a two-step computational design approach, combined with experimental work, to design a highly efficient cocaine hydrolysing enzyme. We engineer E30-6 from human butyrylcholinesterase (BChE), which is specific for cocaine hydrolysis, and obtain a much higher catalytic efficiency for cocaine conversion than for conversion of the natural BChE substrate, acetylcholine (ACh). The catalytic efficiency of E30-6 for cocaine hydrolysis is comparable to that of the most efficient known naturally occurring hydrolytic enzyme, acetylcholinesterase, the catalytic activity of which approaches the diffusion limit. We further show that E30-6 can protect mice from a subsequently administered lethal dose of cocaine, suggesting the enzyme may have therapeutic potential in the setting of cocaine detoxification or cocaine abuse.

Indexed as

AcetylcholinesteraseButyrylcholinesteraseCocaineComputational BiologyHumansHydrolysisAcetylcholinesteraseButyrylcholinesteraseCocaine

Identifiers

PMID24643289
PMCPMC3996704
OpenAlexW2068033427

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.