ArticleJournal of structural biology2010
Towards the understanding of resistance mechanisms in clinically isolated trimethoprim-resistant, methicillin-resistant Staphylococcus aureus dihydrofolate reductase.
Article in Journal of structural biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022Review
- Chiral evasion and stereospecific antifolate resistance in Staphylococcus aureus.PLoS computational biology · 2022Article
- Inhibitor design to target a unique feature in the folate pocket of Staphylococcus aureus dihydrofolate reductase.European journal of medicinal chemistry · 2020Article
- Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.The Journal of antibiotics · 2020Review
- Surface-enhanced Raman scattering method for the identification of methicillin-resistant Staphylococcus aureus using positively charged silver nanoparticles.Mikrochimica acta · 2019Article
- OSPREY Predicts Resistance Mutations Using Positive and Negative Computational Protein Design.Methods in molecular biology (Clifton, N.J.) · 2017Article
- MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates.Cell chemical biology · 2016Article
- Antibacterial Antifolates: From Development through Resistance to the Next Generation.Cold Spring Harbor perspectives in medicine · 2016Review
- Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.ACS medicinal chemistry letters · 2016Article
- Charged Propargyl-Linked Antifolates Reveal Mechanisms of Antifolate Resistance and Inhibit Trimethoprim-Resistant MRSA Strains Possessing Clinically Relevant Mutations.Journal of medicinal chemistry · 2016Article
- Crystal Structures of Trimethoprim-Resistant DfrA1 Rationalize Potent Inhibition by Propargyl-Linked Antifolates.ACS infectious diseases · 2016Article
- Propargyl-Linked Antifolates Are Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis.PloS one · 2016Article
- Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus.Journal of the American Chemical Society · 2015Article
- Protein design algorithms predict viable resistance to an experimental antifolate.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Crystal structures of Klebsiella pneumoniae dihydrofolate reductase bound to propargyl-linked antifolates reveal features for potency and selectivity.Antimicrobial agents and chemotherapy · 2014Article
- Utility of the Biosynthetic Folate Pathway for Targets in Antimicrobial Discovery.Antibiotics (Basel, Switzerland) · 2014Review
- Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.Biochemistry · 2013Article
- Comparative Study of the Frech Catalyst with Two Conventional Catalysts in the Heck Synthesis of 2,4-Diaminopyrimidine-based Antibiotics.Organic preparations and procedures international · 2013Article
- Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase.Biochimica et biophysica acta · 2013Article
- Acetylenic linkers in lead compounds: a study of the stability of the propargyl-linked antifolates.Drug metabolism and disposition: the biological fate of chemicals · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.
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What OpenQuestion holds
Registered trials
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.