Crystal Structures of Klebsiella Pneumoniae Dihydrofolate Reductase Bound to Propargyl-linked Antifolates Reveal Features for Potency and Selectivity

Lamb, K; Lombardo, M; Alverson, J; Priestley, N; Wright, D; Anderson, A

doi:10.1128/AAC.03555-14

Title: Crystal Structures of Klebsiella Pneumoniae Dihydrofolate Reductase Bound to Propargyl-linked Antifolates Reveal Features for Potency and Selectivity

Full Record
Other Related Research

Authors:: Lamb, K; Lombardo, M; Alverson, J; Priestley, N; Wright, D; Anderson, A

Publication Date:: Mon Dec 01 00:00:00 EST 2014

Research Org.:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:: 1228996

Report Number(s):: BNL-111071-2015-JA
Journal ID: ISSN 0066-4804

DOE Contract Number:: SC00112704

Resource Type:: Journal Article

Journal Name:: Antimicrobial Agents and Chemotherapy

Additional Journal Information:: Journal Volume: 58; Journal Issue: 12; Journal ID: ISSN 0066-4804

Country of Publication:: United States

Language:: English

Citation Formats


                    Lamb, K, Lombardo, M, Alverson, J, Priestley, N, Wright, D, and Anderson, A. Crystal Structures of Klebsiella Pneumoniae Dihydrofolate Reductase Bound to Propargyl-linked Antifolates Reveal Features for Potency and Selectivity.  United States: N. p., 2014. 
        Web.  doi:10.1128/AAC.03555-14.

Copy to clipboard


                    Lamb, K, Lombardo, M, Alverson, J, Priestley, N, Wright, D, & Anderson, A. Crystal Structures of Klebsiella Pneumoniae Dihydrofolate Reductase Bound to Propargyl-linked Antifolates Reveal Features for Potency and Selectivity.  United States.  https://doi.org/10.1128/AAC.03555-14

Copy to clipboard


                    Lamb, K, Lombardo, M, Alverson, J, Priestley, N, Wright, D, and Anderson, A. 2014.  
        "Crystal Structures of Klebsiella Pneumoniae Dihydrofolate Reductase Bound to Propargyl-linked Antifolates Reveal Features for Potency and Selectivity".  United States.  https://doi.org/10.1128/AAC.03555-14.

Copy to clipboard


                    
@article{osti_1228996,

  title        = {Crystal Structures of Klebsiella Pneumoniae Dihydrofolate Reductase Bound to Propargyl-linked Antifolates Reveal Features for Potency and Selectivity},

  author       = {Lamb, K and Lombardo, M and Alverson, J and Priestley, N and Wright, D and Anderson, A},

  abstractNote = {},

  doi          = {10.1128/AAC.03555-14},

  url          = {https://www.osti.gov/biblio/1228996},
  journal      = {Antimicrobial Agents and Chemotherapy},

  issn         = {0066-4804},

  number       = 12,

  volume       = 58,

  place        = {United States},

  year         = {Mon Dec 01 00:00:00 EST 2014},

  month        = {Mon Dec 01 00:00:00 EST 2014}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1128/AAC.03555-14

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein–ligand interactions including a structural basis for observed antifolate resistance

Journal Article

An analysis of the protein–ligand interactions in two crystal structures of DHFR-TS from C. hominis reveals a possible structural basis for observed antifolate resistance in C. hominis DHFR. A comparison with the structure of human DHFR reveals residue substitutions that may be exploited for the design of species-selective inhibitors. Cryptosporidium hominis is a protozoan parasite that causes acute gastrointestinal illness. There are no effective therapies for cryptosporidiosis, highlighting the need for new drug-lead discovery. An analysis of the protein–ligand interactions in two crystal structures of dihydrofolate reductase-thymidylate synthase (DHFR-TS) from C. hominis, determined at 2.8 and 2.87 Å resolution, revealsmore »« less
https://doi.org/10.1107/S1744309105002435
Two Crystal Structures of Dihydrofolate Reductase-thymidylate Synthase from Cryptosporidium Hominis Reveal Protein-ligand Interactions Including a Structural Basis for Observed Antifolate Resistance

Journal Article Anderson, A - Acta Cryst.F61:258,2005

No abstract prepared.
Crystal Structures of Wild-type and Mutant Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase Reveal an Alternative Conformation of NADPH that may be Linked to Trimethoprim Resistance

Journal Article Frey, K; Liu, J; Lombardo, M; ... - Journal of Molecular Biology

Both hospital- and community-acquired Staphylococcus aureus infections have become major health concerns in terms of morbidity, suffering and cost. Trimethoprim-sulfamethoxazole (TMP-SMZ) is an alternative treatment for methicillin-resistant S. aureus (MRSA) infections. However, TMP-resistant strains have arisen with point mutations in dihydrofolate reductase (DHFR), the target for TMP. A single point mutation, F98Y, has been shown biochemically to confer the majority of this resistance to TMP. Using a structure-based approach, we have designed a series of novel propargyl-linked DHFR inhibitors that are active against several trimethoprim-resistant enzymes. We screened this series against wild-type and mutant (F98Y) S. aureus DHFR and foundmore »« less
https://doi.org/10.1016/j.jmb.2009.02.045
The crystal structure of a tetrahydrofolate-bound dihydrofolate reductase reveals the origin of slow product release

Journal Article Cao, Hongnan; Gao, Mu; Zhou, Hongyi; ... - Communications Biology
https://doi.org/10.1038/s42003-018-0236-y
Structures of dihydrofolate reductase-thymidylate synthase of Trypanosoma cruzi in the folate-free state and in complex with two antifolate drugs, trimetrexate and methotrexate

Journal Article Senkovich, Olga; Schormann, Norbert; Chattopadhyay, Debasish - Acta Crystallogr. D

The flagellate protozoan parasite Trypanosoma cruzi is the pathogenic agent of Chagas disease (also called American trypanosomiasis), which causes approximately 50 000 deaths annually. The disease is endemic in South and Central America. The parasite is usually transmitted by a blood-feeding insect vector, but can also be transmitted via blood transfusion. In the chronic form, Chagas disease causes severe damage to the heart and other organs. There is no satisfactory treatment for chronic Chagas disease and no vaccine is available. There is an urgent need for the development of chemotherapeutic agents for the treatment of T. cruzi infection and thereforemore »« less
https://doi.org/10.1107/S090744490901230X

Similar Records