Evidence map›Paper›PMID 31886928›Full record

ArticleProtein science : a publication of the Protein Society2020

Structural insights into phosphopantetheinyl hydrolase PptH from Mycobacterium tuberculosis.

John Mosior, Ronnie Bourland, Shivatheja Soma, Carl Nathan, James Sacchettini

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein science : a publication of the Protein Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed, 9 citations in OpenAlex.

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  7. Structural insights into phosphopantetheinyl hydrolase PptH from Mycobacterium tuberculosis.Protein science : a publication of the Protein Society · 2020
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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 2 institutions in 1 country.

John MosiorDepartment of Biochemistry and Biophysics, Texas Agricultural and Mechanical University, College Station, Texas.ORCID 0000-0002-5649-7824
Ronnie BourlandDepartment of Biochemistry and Biophysics, Texas Agricultural and Mechanical University, College Station, Texas.
Shivatheja SomaDepartment of Biochemistry and Biophysics, Texas Agricultural and Mechanical University, College Station, Texas.
Carl NathanDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, New York.
James SacchettiniDepartment of Biochemistry and Biophysics, Texas Agricultural and Mechanical University, College Station, Texas.
Texas College · USCornell University · US

Funding

Vulnerabilities in Mycobacterial Cell-Wall BiogenesisP01AI095208 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI ZHANG, JUNJIE · 2012 to 2022
$19.8M
Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Mycobacterial Phosphopantetheine Hydrolase: Potential for Salvage of Coenzyme AR21AI138939 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI NATHAN, CARL FRANCIS · 2018 to 2019
$466k
NIAID NIH HHS P01 AI095208NIAID NIH HHS R21 AI138939NIGMS NIH HHS P41 GM103311NIH HHS P01AI095208NIH HHS R21 AI138939
6 · The paper itself

Abstract

The amidinourea 8918 was recently reported to inhibit the type II phosphopantetheinyl transferase (PPTase) of Mycobacterium tuberculosis (Mtb), PptT, a potential drug-target that activates synthases and synthetases involved in cell wall biosynthesis and secondary metabolism. Surprisingly, high-level resistance to 8918 occurred in Mtb harboring mutations within the gene adjacent to pptT, rv2795c, highlighting the role of the encoded protein as a potentiator of the bactericidal action of the amidinourea. Those studies revealed that Rv2795c (PptH) is a phosphopantetheinyl (PpT) hydrolase, possessing activity antagonistic with respect to PptT. We have solved the crystal structure of Mtb's phosphopantetheinyl hydrolase, making it the first phosphopantetheinyl (carrier protein) hydrolase structurally characterized. The 2.5 Å structure revealed the hydrolases' four-layer (α/β/β/α) sandwich fold featuring a Mn-Fe binuclear center within the active site. A structural similarity search confirmed that PptH most closely resembles previously characterized metallophosphoesterases (MPEs), particularly within the vicinity of the active site, suggesting that it may utilize a similar catalytic mechanism. In addition, analysis of the structure has allowed for the rationalization of the previously reported PptH mutations associated with 8918-resistance. Notably, differences in the sequences and predicted structural characteristics of the PpT hydrolases PptH of Mtb and E. coli's acyl carrier protein hydrolase (AcpH) indicate that the two enzymes evolved convergently and therefore are representative of two distinct PpT hydrolase families.

Indexed as

Bacterial ProteinsCrystallography, X-RayModels, MolecularMycobacterium tuberculosisProtein ConformationTransferases (Other Substituted Phosphate Groups)Bacterial Proteinsphosphopantetheinyl transferaseTransferases (Other Substituted Phosphate Groups)acyl carrier protein hydrolasedrug resistancemetallophosphoesteraseMycobacterium tuberculosisphosphopantetheinyl hydrolasephosphopantetheinyl transferaseprotein crystallographystructural biology

Identifiers

PMID31886928
PMCPMC7021004
OpenAlexW2998504669

What OpenQuestion holds

Textmetadata
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.