Evidence map›Paper›PMID 42456964›Full record

ArticleJournal of molecular biology2026

The β2αB loop determines NAD(P) cofactor specificity and kinetics in trypanosomal D-3-hydroxybutyrate dehydrogenases.

Hideharu Hashimoto, Ian H Mawn, William Escobar-Arrillaga, Linh Nguyen, Laura A Madigan, Gina Antuono, Tatiana Rossy, Jorna Sojati, Anna Mienko, Erik W Debler and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Hideharu HashimotoDepartment of Biochemistry and Molecular Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Ian H MawnDepartment of Biochemistry and Molecular Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
William Escobar-ArrillagaDepartment of Chemistry and Biochemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA 19085, USA.
Linh NguyenDepartment of Chemistry and Biochemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA 19085, USA.
Laura A MadiganDepartment of Chemistry and Biochemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA 19085, USA.
Gina AntuonoDepartment of Chemistry and Biochemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA 19085, USA.
Tatiana RossyDepartment of Chemistry and Biochemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA 19085, USA.
Jorna SojatiDepartment of Chemistry and Biochemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA 19085, USA.
Anna MienkoDepartment of Biochemistry and Molecular Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Erik W DeblerDepartment of Biochemistry and Molecular Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. Electronic address: Erik.Debler@jefferson.edu.
Jennifer B PalencharDepartment of Chemistry and Biochemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA 19085, USA. Electronic address: jennifer.palenchar@villanova.edu.

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Claudio Guillermo Giraudo · 1995 to 2026
$94.8M
User Training & OutreachP30GM138396 · NIGMS · UCHICAGO ARGONNE, LLC · PI ROBERT F. FISCHETTI, JANET L. SMITH · 2020 to 2026
$34.3M
Chromatin Biology of the African TrypanosomeR01AI165840 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI DEBLER, ERIK · 2022 to 2025
$2.8M
High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APSS10OD012289 · OD · UNIVERSITY OF CHICAGO · PI FISCHETTI, ROBERT F. · 2014 to 2014
$2.0M
A High-Throughput Crystallization Platform at JeffersonS10OD023479 · OD · THOMAS JEFFERSON UNIVERSITY · PI CINGOLANI, GINO · 2019 to 2019
$94k
NCI NIH HHS P30 CA056036NIAID NIH HHS R01 AI165840NIGMS NIH HHS P30 GM138396NIH HHS S10 OD012289NIH HHS S10 OD023479
6 · The paper itself

Abstract

Bacterial d-3-hydroxybutyrate dehydrogenases (HBDHs) catalyze the conversion between d-3-hydroxybutyrate and acetoacetate with NAD as the cofactor but not with NAD 2'-phosphate (NADP). However, HBDHs of the early-branched eukaryotic genus Trypanosoma utilize both NAD and NADP (T. brucei) or exclusively NADP (T. cruzi). Here we reveal that NADP specificity of T. cruzi HBDH arises from stabilization of the flexible β2αB loop by the 2'-phosphate interaction. Stabilization of this loop by a nearby C64Y mutation enables T. cruzi HBDH to use NAD in addition to NADP; thus, the Cys/Tyr residue is critical for determining cofactor specificity in trypanosomal HBDHs, suggesting that most trypanosomal HBDHs use both NAD and NADP except for T. cruzi HBDH. Furthermore, Arg42 within the β2αB loop interacts with the adenine ring of NADP by ideal CH-π interactions, while the R42F mutant switches to non-ideal π-π interactions, increasing k

Indexed as

Hydroxybutyrate DehydrogenaseNADPTrypanosoma cruziKineticsModels, MolecularMutationNADSubstrate SpecificityTrypanosoma brucei bruceiHydroxybutyrate DehydrogenaseNADNADPcoenzymecofactor specificityprotein engineeringtrypanosomex-ray crystal structure

Identifiers

PMID42456964
PMCPMC13455077

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.