Evidence map›Paper›PMID 32389689›Full record

ArticleJournal of molecular biology2020

Structural and Functional Characterization of Phosphatidylinositol-Phosphate Biosynthesis in Mycobacteria.

Meagan Belcher Dufrisne, Carla D Jorge, Cristina G Timóteo, Vasileios I Petrou, Khuram U Ashraf, Surajit Banerjee, Oliver B Clarke, Helena Santos, Filippo Mancia

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

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  13. Mapping the Substrate-Binding Sites in the Phosphatidylserine Synthase inFrontiers in cellular and infection microbiology · 2021
    Article
  14. Review
  15. Article
  16. Article
  17. Host Immune Response and Novel Diagnostic Approach to NTM Infections.International journal of molecular sciences · 2020
    Review
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

9 authors at 3 institutions in 2 countries.

Meagan Belcher DufrisneDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
Carla D JorgeInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República-EAN, 2780-157 Oeiras, Portugal.
Cristina G TimóteoInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República-EAN, 2780-157 Oeiras, Portugal.
Vasileios I PetrouDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
Khuram U AshrafDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
Surajit BanerjeeNE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Argonne, IL 60439, USA.
Oliver B ClarkeDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA; Department of Anesthesiology, Columbia University, New York, NY 10032, USA.
Helena SantosInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República-EAN, 2780-157 Oeiras, Portugal.
Filippo ManciaDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: fm123@cumc.columbia.edu.
Columbia University · USUniversidade Nova de Lisboa · PTArgonne National Laboratory · US

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2M
Y-FAMILY POLYMERASES AND CO-FACTORS IN TRANSLESION REPLICATIONP41RR015301 · NCRR · CORNELL UNIVERSITY ITHACA · PI EISENBERG, DAVID · 2001 to 2011
$28.2M
Training (303-338)P41GM116799 · NIGMS · NEW YORK STRUCTURAL BIOLOGY CENTER · PI HENDRICKSON, WAYNE A. · 2016 to 2020
$7.1M
Structural basis of integral membrane enzyme functionR35GM132120 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Filippo Mancia · 2019 to 2026
$3.7M
Lipid biosynthesis and modification by integral-membrane enzymesR01GM111980 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MANCIA, FILIPPO · 2015 to 2018
$2.2M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
STRUCTURAL BASIS OF AMINORABINOSE BIOSYNTHESIS LINKED TO POLYMYXIN RESISTANCER00GM123228 · NIGMS · RBHS-NEW JERSEY MEDICAL SCHOOL · PI PETROU, VASILEIOS I · 2019 to 2021
$747k
Structural basis of phosphoinositide biosynthesis in Mycobacterium tuberculosisR21AI119672 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MANCIA, FILIPPO · 2015 to 2016
$440k
Structural basis of aminoarabinose biosynthesis linked to polymyxin resistanceK99GM123228 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PETROU, VASILEIOS I · 2017 to 2018
$180k
NCRR NIH HHS P41 RR015301NCRR NIH HHS S10 RR029205NIAID NIH HHS R21 AI119672NIGMS NIH HHS K99 GM123228NIGMS NIH HHS P30 GM124165NIGMS NIH HHS P41 GM116799NIGMS NIH HHS R00 GM123228NIGMS NIH HHS R01 GM111980NIGMS NIH HHS R35 GM132120NIH HHS S10 OD021527
6 · The paper itself

Abstract

In mycobacteria, phosphatidylinositol (PI) acts as a common lipid anchor for key components of the cell wall, including the glycolipids phosphatidylinositol mannoside, lipomannan, and lipoarabinomannan. Glycolipids in Mycobacterium tuberculosis, the causative agent of tuberculosis, are important virulence factors that modulate the host immune response. The identity-defining step in PI biosynthesis in prokaryotes, unique to mycobacteria and few other bacterial species, is the reaction between cytidine diphosphate-diacylglycerol and inositol-phosphate to yield phosphatidylinositol-phosphate, the immediate precursor to PI. This reaction is catalyzed by the cytidine diphosphate-alcohol phosphotransferase phosphatidylinositol-phosphate synthase (PIPS), an essential enzyme for mycobacterial viability. Here we present structures of PIPS from Mycobacterium kansasii with and without evidence of donor and acceptor substrate binding obtained using a crystal engineering approach. PIPS from Mycobacterium kansasii is 86% identical to the ortholog from M. tuberculosis and catalytically active. Functional experiments guided by our structural results allowed us to further characterize the molecular determinants of substrate specificity and catalysis in a new mycobacterial species. This work provides a framework to strengthen our understanding of phosphatidylinositol-phosphate biosynthesis in the context of mycobacterial pathogens.

Indexed as

Bacterial ProteinsBiocatalysisCDP-Diacylglycerol-Inositol 3-PhosphatidyltransferaseModels, MolecularMycobacteriumPhosphatidylinositol PhosphatesProtein ConformationSubstrate SpecificityBacterial ProteinsCDP-Diacylglycerol-Inositol 3-PhosphatidyltransferasePhosphatidylinositol PhosphatesCDP-alcohol phosphotransferasecrystallographyinositol-phosphatetuberculosis

Identifiers

PMID32389689
PMCPMC7483940
OpenAlexW3021083139

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.