Abstract

The objective of the Structural Biology (StructBiol) Core of the Center to Develop Therapeutic Countermeasures to High-threat bacterial Agents is to provide a unique platform for Center investigators to engage in structure-based lead optimization projects by determining the x-ray crystallographic structures of antibacterial agents bound to target protein. The StructBiol Core will help investigators realize the enormous potential of detailed structural Information on ligand-protein interactions for target validation and lead optimization, thereby speeding the antibiotic discovery process.
The specific aims of the StructBiol Core are:
Aim 1 : To provide services for all stages of structural analysis projects from protein expression and purification, biophysical characterization of ligand-target interactions, crystallization and structure determination to structure analysis and presentation.
Aim 2 : To use knowledge gained from structural studies ofthe inhibitor-target protein interactions to increase the binding affinity of lead compounds toward target and improve their pharmacological and chemical properties.

Public Health Relevance

This research is highly relevant for understanding of the structures of antibiotic target sites at a detailed atomic level, and for ultimate discovery of new antibiotics against resistant bacterial infections.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI109713-01
Application #
8655937
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-04-25
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Rutgers University
Department
Type
DUNS #
City
Newark
State
NJ
Country
United States
Zip Code
07103

  Publications

Lane, Thomas; Russo, Daniel P; Zorn, Kimberley M et al. (2018) Comparing and Validating Machine Learning Models for Mycobacterium tuberculosis Drug Discovery. Mol Pharm 15:4346-4360
Papp-Wallace, Krisztina M; Nguyen, Nhu Q; Jacobs, Michael R et al. (2018) Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using ?-Lactamase Inhibitors and ?-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234. J Med Chem 61:4067-4086
Lin, Wei; Das, Kalyan; Degen, David et al. (2018) Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3). Mol Cell 70:60-71.e15
Inoyama, Daigo; Paget, Steven D; Russo, Riccardo et al. (2018) Novel Pyrimidines as Antitubercular Agents. Antimicrob Agents Chemother 62:
Becka, Scott A; Zeiser, Elise T; Barnes, Melissa D et al. (2018) Characterization of the AmpC ?-Lactamase from Burkholderia multivorans. Antimicrob Agents Chemother 62:
Hover, Bradley M; Kim, Seong-Hwan; Katz, Micah et al. (2018) Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens. Nat Microbiol 3:415-422
Barnes, Melissa D; Bethel, Christopher R; Alsop, Jim et al. (2018) Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam. Antimicrob Agents Chemother 62:
Kumar, Pradeep; Capodagli, Glenn C; Awasthi, Divya et al. (2018) Synergistic Lethality of a Binary Inhibitor of Mycobacterium tuberculosis KasA. MBio 9:
Nukaga, Michiyoshi; Papp-Wallace, Krisztina M; Hoshino, Tyuji et al. (2018) Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam. Antimicrob Agents Chemother 62:
Becka, Scott A; Zeiser, Elise T; Marshall, Steven H et al. (2018) Sequence heterogeneity of the PenA carbapenemase in clinical isolates of Burkholderia multivorans. Diagn Microbiol Infect Dis 92:253-258

Showing the most recent 10 out of 23 publications