Evidence map›Paper›PMID 41972430›Full record

ArticleBiochemistry2026

Aromatic Residues in Mobile Regions Distal to the Active Site Support the Closed Conformation of

Lydia J Kramer, Steven L Austin, Ananya Majumdar, Noah D Smith, H Lee Woodcock, Caren L Freel Meyers

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Lydia J KramerDepartment of Physiology, Pharmacology, and Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
Steven L AustinDivision of Natural Sciences, New College of Florida, Sarasota, Florida 34243, United States.
Ananya MajumdarBiomolecular NMR Center, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Noah D SmithDepartment of Physiology, Pharmacology, and Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
H Lee WoodcockDepartment of Chemistry, University of South Florida, Tampa, Florida 33620, United States.ORCID 0000-0003-3539-273X
Caren L Freel MeyersDepartment of Physiology, Pharmacology, and Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.ORCID 0000-0003-1458-0897

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Toward Understanding the Chemistry and Biology of Microbial DXP SynthaseR01GM143810 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Caren L. Freel Meyers · 2021 to 2026
$2.0M
The Chemistry-Biology Interface Program at Johns Hopkins UniversityT32GM149382 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI STEVEN E ROKITA · 2023 to 2026
$1.4M
Acquisition of a 500 MHz NMR Spectrometer to Support Small-Molecule Chemistry at Johns Hopkins Medical SchoolS10OD034217 · OD · JOHNS HOPKINS UNIVERSITY · PI BHAT, SHRIDHAR · 2024 to 2024
$425k
NIGMS NIH HHS R01 GM143810NIGMS NIH HHS T32 GM007445NIGMS NIH HHS T32 GM149382NIH HHS S10 OD034217
6 · The paper itself

Abstract

The essential bacterial enzyme 1-deoxy-d-xylulose 5-phosphate synthase (DXPS) is absent in humans, making the enzyme an attractive antimicrobial target. Its product DXP sits at a metabolic branchpoint and is required for biosynthesis of pyridoxal phosphate (PLP), thiamin diphosphate (ThDP), and isoprenoids. DXP is formed via decarboxylation of pyruvate and subsequent carboligation with d-glyceraldehyde-3-phosphate (d-GAP) in a ThDP-dependent manner. In the current mechanistic model, DXPS follows a ligand-gated mechanism. Pyruvate reacts with ThDP to form C2α-lactylThDP (LThDP), which coincides with a shift to a closed conformation. The flexible "spoon" and "fork" motifs become ordered and the catalytic residue H299 is placed within the active site, supporting LThDP formation and persistence in the closed conformation of the E-LThDP complex until binding of d-GAP. We aim to understand the molecular basis for stabilization of the E-LThDP complex in its closed conformation. We propose that the conserved aromatic residues Y288, F298, and F304 in the

Indexed as

Amino Acids, AromaticEscherichia coliEscherichia coli ProteinsTransferasesCatalytic DomainModels, MolecularProtein ConformationAmino Acids, Aromaticdeoxyxylulose-5-phosphate synthaseEscherichia coli ProteinsTransferases

Identifiers

PMID41972430
PMCPMC13173681

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.