Our laboratory uses nuclear magnetic resonance (NMR) to study modulations of protein dynamics and conformations in active enzymatic systems.
Non-ribosomal peptide synthetases (NRPSs) are large enzymatic systems responsible for the biosynthesis of a wealth of secondary metabolites, many of which are used by pharmaceutical scientists to produce drugs such as antibiotics or anticancer agents. To synthesize all of these remarkably diverse compounds, bacteria and fungi use a surprisingly conserved strategy: NRPSs are organized in modules, made of conserved domains, that each incorporates a dedicated substrate. Thus, new compounds with improved activities can be generated, in principle, by swapping domains or modules in order to control substrate incorporation and hence the final product. To do this efficiently, a deep understanding of domain communication during the synthesis is required. NMR and crystallography studies indicate that domain interactions are transient and that their quaternary structure is likely subject to rearrangements during the synthesis. In addition, both techniques show that individual domains are subject to conformational heterogeneity. We principally use NMR to investigate inter- and intra-domain modifications occurring during the catalytic steps of non-ribosomal peptide synthesis.
Dr. Aswani K. Kancherla
Dr. Indrani Pal
Dr. Subrata H. Mishra
We are located at the 7th floor of the Hunterian building at the Johns Hopkins School of Medicine, in Baltimore, Maryland. Enter the building from the intersection between N. Wolfe Street and Monument Street, at the corner featuring a little courtyard.
We manage a 600 MHz Bruker AVANCEIII spectrometer equipped with a QCI-cryoprobe, located in the sub-basement of our building. We are part of the Johns Hopkins Biomolecular NMR center, located at the Johns Hopkins Homewood campus (15 min. drive) and housing two more 600 MHz spectrometers and an 800 MHz spectrometer, all equipped with cryoprobes.
725 N. Wolfe street
Johns Hopkins School of Medicine,
Baltimore, MD, 21205
Lab phone: 410 614 2229