Nadine Samara, PhD
Structural Biochemistry Unit
30 Convent Dr. MSC 4370
Bethesda MD 20892
Glycans (or polysaccharides) that are covalently linked to proteins and lipids modulate the host-microbe interface in the oral cavity and play an important role in health and disease. From microbe to host, glycan biosynthesis is catalyzed by a diverse family of enzymes called glycosyltransferases (GTs).
In the host
We study a family of GTs termed Polypeptide N-Acetylgalactosaminyltransferase (GalNAc-Ts) that initiate mucin-type O-glycosylation by transferring N-Acetylgalactosamine (GalNAc) from UDP-GalNAc to Thr/Ser residues of a protein substrate. Substrates include the mucin glycoproteins that endow the mucus lining the surface of the epithelium gel-like properties that are vital for protecting the underlying tissue from deleterious infection as well as physical and chemical damage. The glycan chains on mucus also underlie the persistence of many commensal bacteria. Our lab uses structural and biochemical methods to answer the following questions:
- How do GalNAc-Ts recognize substrates? Specific substrates for many GalNAc-Ts have not been identified because the enzymes do not recognize a single consensus sequence or motif. To identify their substrates and better understand their biological functions, we are investigating the molecular basis of substrate preferences.
- What is the mechanism of active site alignment and catalysis? Our ultimate goal is to identify small molecule modulators of GalNAc-Ts to enable enhancement of those activities beneficial for health and to inhibit those which are harmful.
We study GTs that synthesize virulence factors in microbes that reside in the oral cavity. These factors include:
- Lipopolysaccharides (LPS, endotoxins) consisting of lipid A, core oligosaccharides, and O-polysaccharides (O-antigen). LPS coat the outer membrane of gram-negative bacteria and can elicit a strong immune response in the host. We are interested in understanding the mechanism of O-polysaccharide biosynthesis.
- Capsular polysaccharides (CPS) that coat the outer membranes of some bacteria and help them to evade host defenses such as phagocytosis. Currently, we are interested in GTs that synthesize CPS containing GalNAc and want to understand how these enzymes are evolutionarily distinct from metazoan GalNAc-Ts.
- Exopolysaccharides (EPS) are involved in biofilm formation. How are these structures synthesized?
Understanding the synthesis machinery of these molecules will help to identify potential antimicrobial targets.
Dr. Nadine Samara was born in New York City and has lived in Lebanon, Saudi Arabia and the United States. Upon graduating from the American University of Beirut with a B.S. in Chemistry, she returned to the United States and obtained a Ph.D. in Molecular Biophysics from The Johns Hopkins University School of Medicine. She then started her postdoctoral research as an NIGMS-PRAT Fellow at NIDDK/NIH. In 2015, Dr. Samara transitioned to a Staff Scientist Position at NIDCR/NIH, where she is now an Earl Stadtman Investigator and Chief of the Structural Biochemistry Unit. As a Distinguished Scholar at NIH, Dr. Samara will focus on building an inclusive and diverse environment within the lab and institute.
May C, Ji S, Syed ZA, Revoredo L, Daniel EJP, Gerken TA, Tabak LA, Samara NL, Ten Hagen KG. Differential splicing of the lectin domain of an O-glycosyltransferase modulates both peptide and glycopeptide preferences. J Biol Chem. 2020.
Fernandez AJ, Daniel EJP, Mahajan SP, Gray JJ, Gerken TA, Tabak LA, Samara NL. The structure of the colorectal cancer-associated enzyme GalNAc-T12 reveals how nonconserved residues dictate its function. Proc Natl Acad Sci U S A. 2019;116(41):20404-20410.
Wu J, Samara NL, Kuraoka I, Yang W. Evolution of Inosine-Specific Endonuclease V from Bacterial DNase to Eukaryotic RNase. Mol Cell. 2019;76(1):44-56.e3.
Samara NL, Yang W. Cation trafficking propels RNA hydrolysis. Nat Struct Mol Biol. 2018;25(8):715-721.
Ji S, Samara NL, Revoredo L, Zhang L, Tran DT, Muirhead K, Tabak LA, Ten Hagen KG. A molecular switch orchestrates enzyme specificity and secretory granule morphology. Nat Commun. 2018;9(1):3508.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Microbiology and Infectious Diseases
This page was last updated on October 9th, 2019