Evidence map›Paper›PMID 31034887›Full record

ArticleJournal of molecular biology2019

Fitness Effects of Single Amino Acid Insertions and Deletions in TEM-1 β-Lactamase.

Courtney E Gonzalez, Paul Roberts, Marc Ostermeier

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 51 citations in OpenAlex.

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  8. Structural and energetic analysis of stabilizing indel mutations.bioRxiv : the preprint server for biology · 2024
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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

3 authors at 1 institution in 1 country.

Courtney E GonzalezDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Paul RobertsDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Marc OstermeierDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA. Electronic address: oster@jhu.edu.
Johns Hopkins University · US

Funding

Experimentally-determined fitness landscape of beta-lactamase inhibitory proteinF31GM101941 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GONZALEZ, COURTNEY ELAINE · 2012 to 2015
$170k
NIGMS NIH HHS F31 GM101941
6 · The paper itself

Abstract

Short insertions and deletions (InDels) are a common type of mutation found in nature and a useful source of variation in protein engineering. InDel events have important consequences in protein evolution, often opening new pathways for adaptation. However, much less is known about the effects of InDels compared to point mutations and amino acid substitutions. In particular, deep mutagenesis studies on the distribution of fitness effects of mutations have focused almost exclusively on amino acid substitutions. Here, we present a near-comprehensive analysis of the fitness effects of single amino acid InDels in TEM-1 β-lactamase. While we found InDels to be largely deleterious, partially overlapping deletion-tolerant and insertion-tolerant regions were observed throughout the protein, especially in unstructured regions and at the end of helices. The signal sequence of TEM-1 tolerated InDels more than the mature protein. Most regions of the protein tolerated insertions more than deletions, but a few regions tolerated deletions more than insertions. We examined the relationship between InDel tolerance and a variety of measures to help understand its origin. These measures included evolutionary variation in β-lactamases, secondary structure identity, tolerance to amino acid substitutions, solvent accessibility, and side-chain weighted contact number. We found secondary structure, weighted contact number, and evolutionary variation in class A beta-lactamases to be the somewhat predictive of InDel fitness effects.

Indexed as

INDEL MutationAmino Acid Substitutionbeta-LactamasesDrug Resistance, BacterialEscherichia coliEscherichia coli InfectionsEscherichia coli ProteinsHumansModels, MolecularProtein Conformationbeta-Lactamasesbeta-lactamase TEM-1Escherichia coli Proteinsantibiotic resistance proteinfitness landscapesInDelsprotein evolution

Identifiers

PMID31034887
PMCPMC6554054
OpenAlexW2940885779

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.