Evidence map›Paper›PMID 31191864›Full record

ArticleMedChemComm2019

How mithramycin stereochemistry dictates its structure and DNA binding function.

Caixia Hou, Jürgen Rohr, Sean Parkin, Oleg V Tsodikov

Open access · bronzeAbstract read
In one paragraph

Article in MedChemComm, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Practical hints and tips for solution of pseudo-merohedric twins: three case studies.Acta crystallographica. Section E, Crystallographic communications · 2021
    Article
  6. Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis.Angewandte Chemie (International ed. in English) · 2020
    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

4 authors at 1 institution in 1 country.

Caixia HouUniversity of Kentucky , Department of Pharmaceutical Sciences , College of Pharmacy , Lexington , KY 40536-0596 , USA . Email: oleg.tsodikov@uky.edu ; Email: jrohr2@uky.edu.
Jürgen RohrUniversity of Kentucky , Department of Pharmaceutical Sciences , College of Pharmacy , Lexington , KY 40536-0596 , USA . Email: oleg.tsodikov@uky.edu ; Email: jrohr2@uky.edu.
Sean ParkinUniversity of Kentucky , Department of Chemistry , Lexington , KY 40506-0055 , USA . Email: s.parkin@uky.edu.
Oleg V TsodikovUniversity of Kentucky , Department of Pharmaceutical Sciences , College of Pharmacy , Lexington , KY 40536-0596 , USA . Email: oleg.tsodikov@uky.edu ; Email: jrohr2@uky.edu.ORCID 0000-0001-7094-4216
University of Kentucky · US

Funding

NOVEL AUREOLIC ACID TYPE ANTITUMOR AGENTSR01CA091901 · NCI · UNIVERSITY OF KENTUCKY · PI ROHR, JURGEN T · 2001 to 2017
$3.6M
NCI NIH HHS R01 CA091901
6 · The paper itself

Abstract

An aureolic acid natural product mithramycin (MTM) has been known for its potent antineoplastic properties. MTM inhibits cell growth by binding in the minor groove of double-stranded DNA as a dimer, in which the two molecules of MTM are coordinated to each other through a divalent metal ion. A crystal structure of an MTM analogue, MTM SA-Phe, in the active metal ion-coordinated dimeric form demonstrates how the stereochemical features of MTM define the helicity of the dimeric scaffold for its binding to a right-handed DNA double helix. We also show crystallographically and biochemically that MTM, but not MTM SA-Phe, can be inactivated by boric acid through formation of a large macrocyclic species, in which two molecules of MTM are crosslinked to each other through 3-side chain-boron-sugar intermolecular bonds. We discuss these structural and biochemical properties in the context of MTM biosynthesis and the design of MTM analogues as anticancer therapeutics.

Identifiers

PMID31191864
PMCPMC6533888
OpenAlexW2932830013

What OpenQuestion holds

Textmetadata
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.