Evidence map›Paper›PMID 36481732›Full record

ArticleNature communications2022

Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases.

Yuya Nishida, Sachiko Yanagisawa, Rikuri Morita, Hideki Shigematsu, Kyoko Shinzawa-Itoh, Hitomi Yuki, Satoshi Ogasawara, Ken Shimuta, Takashi Iwamoto, Chisa Nakabayashi and 24 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 44% 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

1 citing paper in PubMed, 9 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 10 institutions in 1 country.

Yuya NishidaDepartment of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.ORCID 0000-0002-1994-0807
Sachiko Yanagisawa *Graduate School of Science, University of Hyogo, Hyogo, Japan.ORCID 0000-0003-3688-797X
Rikuri Morita *Center for Computational Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.ORCID 0000-0002-0465-5528
Hideki ShigematsuRIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo, Japan.ORCID 0000-0003-3951-8651
Kyoko Shinzawa-ItohGraduate School of Science, University of Hyogo, Hyogo, Japan.
Hitomi YukiRIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.ORCID 0000-0002-8778-8261
Satoshi OgasawaraDepartment of Chemistry, Graduate School of Science, Chiba University, Inage, Chiba, Japan.
Ken ShimutaDepartment of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
Takashi IwamotoDepartment of Medical Biochemistry, Osaka University Graduate School of Frontier Biological Science, Suita, Osaka, Japan.
Chisa NakabayashiDepartment of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Waka MatsumuraGraduate School of Science, University of Hyogo, Hyogo, Japan.
Hisakazu KatoDepartment of Medical Biochemistry, Osaka University Graduate School of Frontier Biological Science, Suita, Osaka, Japan.
Chai GopalasingamRIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo, Japan.
Takemasa NagaoDepartment of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Tasneem QaqorhDepartment of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.ORCID 0000-0002-3506-5870
Yusuke TakahashiDepartment of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Satoru YamazakiDepartment of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Katsumasa KamiyaCenter for Basic Education Integrated Learning, Kanagawa Institute of Technology, Atsugi, Kanagawa, Japan.
Ryuhei HaradaCenter for Computational Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.ORCID 0000-0001-7987-0540
Nobuhiro MizunoProtein Crystal Analysis Division, Japan Synchrotron Radiation Research Institute, SPring-8, Sayo, Hyogo, Japan.ORCID 0000-0003-1632-8556
Hideyuki TakahashiDepartment of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
Yukihiro AkedaDepartment of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
Makoto OhnishiDepartment of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
Yoshikazu IshiiDepartment of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
Takashi KumasakaProtein Crystal Analysis Division, Japan Synchrotron Radiation Research Institute, SPring-8, Sayo, Hyogo, Japan.ORCID 0000-0001-9289-1557
Takeshi MurataDepartment of Chemistry, Graduate School of Science, Chiba University, Inage, Chiba, Japan.ORCID 0000-0002-5748-4670
Kazumasa MuramotoGraduate School of Science, University of Hyogo, Hyogo, Japan.
Takehiko ToshaRIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo, Japan.ORCID 0000-0002-8971-0759
Yoshitsugu ShiroGraduate School of Science, University of Hyogo, Hyogo, Japan.ORCID 0000-0003-0695-8327
Teruki HonmaRIKEN Center for Biosystems Dynamics Research, Yokohama, Kanagawa, Japan.
Yasuteru ShigetaCenter for Computational Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.ORCID 0000-0002-3219-6007
Minoru KuboGraduate School of Science, University of Hyogo, Hyogo, Japan.ORCID 0000-0002-1470-942X
Seiji TakashimaDepartment of Medical Biochemistry, Osaka University Graduate School of Frontier Biological Science, Suita, Osaka, Japan.
Yasunori ShintaniDepartment of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. shintani.yasunori@ncvc.go.jp.ORCID 0000-0001-9579-0727
National Cerebral and Cardiovascular Center · JPUniversity of Hyogo · JPSPring-8 · JPNational Institute of Infectious Diseases · JPThe University of Osaka · JPUniversity of Tsukuba · JPChiba University · JPRIKEN Center for Biosystems Dynamics Research · JPKanagawa Institute of Technology · JPToho University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to rise and would become untreatable. The development of antibiotics with a different mechanism of action is seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), the essential respiratory enzymes for life. The steric conformation around the binding pocket of HCOs is highly conserved among bacteria and eukaryotes, yet the latter has an extra helix. This structural difference in the conserved allostery enabled us to rationally identify bacterial HCO-specific inhibitors: an antibiotic compound against ceftriaxone-resistant Neisseria gonorrhoeae. Molecular dynamics combined with resonance Raman spectroscopy and stopped-flow spectroscopy revealed an allosteric obstruction in the substrate accessing channel as a mechanism of inhibition. Our approach opens fresh avenues in modulating protein functions and broadens our options to overcome AMR.

Indexed as

Anti-Bacterial AgentsHemeAnti-Bacterial AgentsHeme

Identifiers

PMID36481732
PMCPMC9731990
OpenAlexW4312193009

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.