Department of Chemistry
725 21st Street, NW | Corcoran 107
Washington, DC 20052
Phone: (202) 994-6121
Fax: (202) 994-5873
E-mail: [email protected]
Web:
http://departments.columbian.gwu.edu/chemistry
Department of Chemistry Seminars
“Probing Calreticulin Function Via Lysine Acylation”
Calreticulin (CRT) is a protein found mainly in the endoplasmic reticulum (ER) that maintains calcium levels and
controls protein folding, but has also been recently found at the cell surface, cytoplasm, and in the extracellular
matrix. CRT participates in multiple physiological processes such as gene expression, immune response, and cancer.
Calreticulin has been shown to autoacetylate with the binding of preferred ligand 7,8-diacetoxy-4-methylcoumarin
(DAMC). Ongoing research aims to develop a chemical biology approach to tease out the importance of CRT
acylating abilities on both its endoplasmic and non-endoplasmic reticulum functions by targeting the downstream
substrates of CRT acetylation. A “bump-hole” approach will be used to explore the acetyltransferase abilities of CRT.
Our goal is to modify CRT to transfer a pentynoyl tag (using a redesigned ligand) to its substrates, which can then be
used as a handle for protein identification. Modifying CRT to perform pentynoylation requires structural data of the
wild type protein. The crystal structure of full length CRT has yet to be solved, therefore, molecular modeling using
available data in the literature (such as protein homology and NMR data) has been used to approximate the binding
interface between CRT and the acylation ligands. Molecular Operating Environment (MOE) software was used to
perform sequence alignment, simulated annealing, positional refinement, as well as blind docking of the binding
interaction of acyloxycoumarins with the CRT model.
Lystranne Maynard--‐Smith is an Assistant Professor in the Chemistry
Department of Howard University. She received her B.Sc. from Howard
University in 1999, and completed her Ph.D. at Stanford University in 2006 with
Tom Wandless, where she worked on the destabilizing domain project. This was
followed by a postdoctoral position at the National Institutes of Health with Hans
Luecke in the NIDDK institute where she worked on histone acetyltransferases.
In 2010, Lystranne joined the faculty at Howard University where she currently
teaches biochemistry, organic chemistry and conducts research in the chemical
biology field.
Prof. Lystranne Maynard-Smith
Assistant Professor of Chemistry
Department of Chemistry
Howard University
Friday, February 7, 2014
Corcoran Hall, Room 101
3:00 – 4:00 p.m.
Refreshments will be served at 2:45 p.m.