A Structural Basis for 129Xe Hyper-CEST Signal in TEM-1 β-Lactamase

Roose, Benjamin W.; Zemerov, Serge D.; Wang, Yanfei; Kasimova, Marina A.; Carnevale, Vincenzo; Dmochowski, Ivan J.

doi:10.1002/cphc.201800624

A Structural Basis for ¹²⁹Xe Hyper-CEST Signal in TEM-1 β-Lactamase

Journal Article · Thu Sep 13 00:00:00 EDT 2018 · ChemPhysChem

DOI:https://doi.org/10.1002/cphc.201800624· OSTI ID:1569911

^[1]; Zemerov, Serge D. ^[1]; Wang, Yanfei ^[2]; ^[3]; Carnevale, Vincenzo ^[4]; ^[1]

Univ. of Pennsylvania, Philadelphia, PA (United States)
Harvard Medical School, Boston, MA (United States)
KTH Royal Inst. of Technology, Stockholm (Sweden)
Temple Univ., Philadelphia, PA (United States)

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, we performed structural and computational studies 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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: National Institutes of Health (NIH); USDOD; USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357; AC02-76SF00515; SC0012704

OSTI ID:: 1569911

Journal Information:: ChemPhysChem, Journal Name: ChemPhysChem Journal Issue: 2 Vol. 20; ISSN 1439-4235

Publisher:: ChemPubSoc EuropeCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
CEST
contrast
hyperpolarized
magnetic resonance
xenon