A Structural Basis for 129Xe Hyper‐CEST Signal in TEM‐1 β‐Lactamase
Abstract
Genetically encoded (GE) contrast agents detectable by magnetic resonance imaging (MRI) enable non‐invasive visualization of gene expression and cell proliferation at virtually unlimited penetration depths. Using hyperpolarized 129Xe in combination with chemical exchange saturation transfer, an MR contrast approach known as hyper‐CEST, enables ultrasensitive protein detection and biomolecular imaging. GE MRI contrast agents developed to date include nanoscale proteinaceous gas vesicles as well as the monomeric bacterial proteins TEM‐1 β‐lactamase (bla) and maltose binding protein (MBP). To improve understanding of hyper‐CEST NMR with proteins, structural and computational studies were performed to further characterize the Xe‐bla interaction. X‐ray crystallography validated the location of a high‐occupancy Xe binding site predicted by MD simulations, and mutagenesis experiments confirmed this Xe site as the origin of the observed CEST contrast. Structural studies and MD simulations with representative bla mutants offered additional insight regarding the relationship between local protein structure and CEST contrast.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 13, 2018
- Source ID
- 10.1002/cphc.201800624
Entities
People
- Benjamin W Roose
- Ivan J Dmochowski
- Marina A Kasimova
- Serge D. Zemerov
- Vincenzo Carnevale
- Yanfei Wang
Organizations
- Harvard Medical School
- National Institutes of Health
- Royal Institute of Technology
- Temple University
- University of Pennsylvania