Evidence map›Paper›PMID 34095235›Full record

ArticleFrontiers in molecular biosciences2021

Modulating Enzyme Function

Jasmina S Redzic, Michael R Duff, Ashley Blue, Todd M Pitts, Pratul Agarwal, Elan Zohar Eisenmesser

Open access · goldAbstract read
In one paragraph

Article in Frontiers in molecular biosciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

9 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Protein dynamics: The future is bright and complicated!Structural dynamics (Melville, N.Y.) · 2023
    Article
  8. Inducible SystemicInternational journal of molecular sciences · 2022
    Article
  9. Article
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

6 authors at 5 institutions in 1 country.

Jasmina S RedzicDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Denver, CO, United States.
Michael R DuffBiochemistry and Cellular and Molecular Biology Department, University of Tennessee, Knoxville, TN, United States.
Ashley BlueNational High Magnetic Field Laboratory, Tallahassee, FL, United States.
Todd M PittsDivision of Medical Oncology, School of Medicine, University of Colorado, Aurora, CO, United States.
Pratul AgarwalDepartment of Physiological Sciences and High Performance Computing Center, Oklahoma State University, Stillwater, OK, United States.
Elan Zohar EisenmesserDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Denver, CO, United States.
University of Colorado Denver · USNational High Magnetic Field Laboratory · USOklahoma State University · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Tennessee at Knoxville · US

Funding

The global regulation of dynamics and structure mediated by single hydride in a family of reductasesR01GM139892 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI EISENMESSER, ELAN Z · 2021 to 2024
$1.2M
NIGMS NIH HHS R01 GM139892
6 · The paper itself

Abstract

The biliverdin reductase B (BLVRB) class of enzymes catalyze the NADPH-dependent reduction of multiple flavin substrates and are emerging as critical players in cellular redox regulation. However, the role of dynamics and allostery have not been addressed, prompting studies here that have revealed a position 15 Å away from the active site within human BLVRB (T164) that is inherently dynamic and can be mutated to control global micro-millisecond motions and function. By comparing the inherent dynamics through nuclear magnetic resonance (NMR) relaxation approaches of evolutionarily distinct BLVRB homologues and by applying our previously developed Relaxation And Single Site Multiple Mutations (RASSMM) approach that monitors both the functional and dynamic effects of multiple mutations to the single T164 site, we have discovered that the most dramatic mutagenic effects coincide with evolutionary changes and these modulate coenzyme binding. Thus, evolutionarily changing sites distal to the active site serve as dynamic "dials" to globally modulate motions and function. Despite the distal dynamic and functional coupling modulated by this site, micro-millisecond motions span an order of magnitude in their apparent kinetic rates of motions. Thus, global dynamics within BLVRB are a collection of partially coupled motions tied to catalytic function.

Indexed as

allosterycouplingdynamicsenzymeNMRreductase

Identifiers

PMID34095235
PMCPMC8173106
OpenAlexW3163356825

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.