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Melissa Liriano Vyfhuis, MD/Ph.D.


Chemistry and Biochemistry 2012

Area of Doctoral Study: Biochemistry, MD/Ph.D Program, UMB

Undergraduate Institute: University of Maryland, Baltimore County
Research Advisor : David Weber, Ph.D.

Current Position: Resident, University of Maryland Medical Center – Midtown Campus (Radiation Oncology)

Description of Research

The S100 family is a class of small, homodimeric proteins that are often characterized by their Ca2+-dependent biological effects, which is typically the result of a calcium-dependent conformational change. To characterize whether S100A5 undergoes a conformational change similar to that observed in other S100 proteins, we will first determine the high resolution structure of this protein by NMR in the absence (Aim 1) and presence of calcium (Aim 2). Although human S100A5 shares approximately 50% sequence homology with all the other S100 proteins, it binds to Ca2+ with an affinity 10-100 times greater then any other in the S100 protein family. Therefore, we next plan to examine how S100A5 binds calcium more tightly, which is important for understanding the biological function of S100A5 and its calcium-dependent interaction with target proteins. We hypothesize that the high affinity of S100A5 is due to either a structural difference between S100A5 and other S100 proteins (i.e. an additional ligand) or that S100A5 lacks the dynamic properties observed in the C-terminal region of other S100 proteins that could contribute to their lesser affinity for calcium. In order to elucidate which mechanism is the basis of A5’s high affinity for Ca2+, we propose to also solve the Ca2+-bound S100A5 using X-ray crystallography (Aim 2) to determine if there is an additional Ca2+ ion ligand in the coordination sphere (at position 9 of the EF-hand) that is observed in parvalbumin but not in other S100 proteins. Internal dynamics will also be measured using 15N NMR relaxation methods to prove whether or not S100A5 lacks dynamic properties in the C-terminal helix-loop-helix EF-hand calcium binding domain that could also contribute to its higher affinity for calcium (Aim 3).