Evidence map›Paper›PMID 33199204›Full record

ArticleBioorganic & medicinal chemistry2021

Bisubstrate inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: Transition state analogs for high affinity binding.

Genbin Shi, Gary X Shaw, Fengxia Zhu, Sergey G Tarasov, Xinhua Ji

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

Article in Bioorganic & medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 33% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Assay Development and Identification of the FirstMolecules (Basel, Switzerland) · 2022
    Article
  3. Virtual screening andRSC medicinal chemistry · 2021
    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

5 authors at 2 institutions in 1 country.

Genbin ShiMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA.
Gary X ShawMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA.
Fengxia ZhuMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA; School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaiyin, Jiangsu Province, China(1).
Sergey G TarasovStructural Biophysics Laboratory, National Cancer Institute, Frederick, MD, USA.
Xinhua JiMacromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: jix@mail.nih.gov.
National Cancer Institute · USFrederick National Laboratory for Cancer Research · US

Funding

Biomolecular Structure and Mechanism, Structure-Based Drug DesignZIABC010326 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI JI, XINHUA · 2009 to 2024
$27.3M
CCR Biophysics Resource CoreZICBC010965 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TARASOV, SERGEY · 2009 to 2025
$10.5M
Intramural NIH HHS ZIA BC010326
6 · The paper itself

Abstract

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate biosynthesis pathway. It catalyzes pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). HPPK is essential for microorganisms but absent in mammals; therefore, it is an attractive target for developing novel antimicrobial agents. Previously, based on our studies of the structure and mechanism of HPPK, we created first-generation bisubstrate inhibitors by linking 6-hydroxymethylpterin to adenosine through phosphate groups, and developed second-generation inhibitors by replacing the phosphate bridge with a linkage that contains a piperidine moiety. Here, we report third-generation inhibitors designed based on the piperidine-containing inhibitor, mimicking the transition state. We synthesized two such inhibitors, characterized their protein-binding and enzyme inhibition properties, and determined their crystal structures in complex with HPPK, advancing the development of such bisubstrate analog inhibitors.

Indexed as

Adenosine TriphosphateBinding SitesCrystallography, X-RayDiphosphotransferasesDose-Response Relationship, DrugEnzyme InhibitorsEscherichia coliModels, MolecularMolecular StructurePiperidinesPterinsStructure-Activity Relationship2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase6-hydroxymethyl-7,8-dihydropterinAdenosine TriphosphateDiphosphotransferasesEnzyme InhibitorspiperidinePiperidinesPterinsAntibacterialBisubstrate inhibitorFolateHPPKPterinTransition state analog

Identifiers

PMID33199204
PMCPMC7855645
OpenAlexW3105193730

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.