M. Sundaramoorthy (Sundar)

Protein structure-function, matrix biology and sialic acid biosynthesis

The general research interest of our lab is structure-function studies of proteins focusing on two major areas: (1) Collagen synthesis and assembly and (2) infectious disease and rational drug design. The lab uses techniques in molecular biology, protein chemistry, x-ray crystallography and molecular modeling, and other biophysical methods.

The first project involves the study of noncollagenous domains and post-translational modifications in collagens. Collagens are a family of extracellular matrix proteins that play a dominant role in maintaining the structural integrity of various organs and tissues. They have several other important biological functions such as wound healing and cell differentiation. The folding and assembly of collagens involve unique post-translational modifications of the collagen polypeptides and chain specificity encoded in their noncollagenous domains. Recently we determined the first crystal structure of NC1 domains of type IV collagen. The NC1 domains facilitate the initial chain recognition and assembly of type IV collagen network. Two important renal diseases, Goodpasture syndrome and Alport syndrome, are directly linked to this protein. Type IV collagen is a major structural protein component of basement membrane, which exits as six isoforms, a1-a6 forming three distinct networks¿a1.a2 (ubiquitous), a3.a4.a5 (kidney glomerulus), and a1.a2-a5.a6 (smooth muscle cell).

The second project focuses on the enzymes involved in the sialic acid biosynthetic pathways in pathogenic bacteria and human. The lipopolysaccharides of few Gram negative bacteria mimic human cell surface polysialic acid. This molecular mimicry helps bacteria to evade the host¿s immune system and establish infection causing such diseases as meningitis and septicemia. Our long term goal is to accumulate a wealth of structural and biochemical data on these enzymes for designing new generation of antibiotics against certain pathogens. We also study enzymes responsible for drug activation and resistance in Mycobacterium tuberculosis with the goal of re-engineering the drugs that are active against both resistant and non-resistant strains.

Lab Homepage