Exploring the Sulfatase 1 Catch Bond Free Energy Landscape using Jarzynski's Equality

Abstract

Common yeast Candida albicans as a wild-type cell presents an ovoid shape; in its pathogenic morphology, C. albicans develops a germ tube which develops into a hypha. Development of a hypha is theorized to act as a mechanism for cell survival in less-than optimal environments, such as within the human body. In addition to human serum inducing hyphal growth, C. albicans' development of hyphae occurs when the cells are under stress, in basic pH, or exposed to a variety of amino acids. While the environments in which hyphae form are well known, the biomechanical changes associated with this transition are less investigated. Our technique combines the use of an atomic force microscope in contact mode with its force-distance spectroscopy capability to determine the cell stiffness of C. albicans in its various morphological states. By measuring cell stiffness in both the cytosol and nucleus for wild-type form and pseudohyphal morphology, and in cytosol and hypha for the hyphal morphology, we are able to determine the degree by which the cell loses its pliability as it assumes pathogenicity. Because of these implications of hyphal growth, we expect the stiffness of C. albicans to be significantly higher than that of its pseudohyphal morphology or wild-type form.

Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity

“…Furin cleavage (Tang and Rosen, 2009) and N-glycosylations (Ambasta et al, 2007;Seffouh et al, 2019b) may be dispensable for the enzyme activity but play a role in the enzyme attachment to the cell surface, while conversion of C 88 into an FGly residue is a hallmark of all sulfatases and is essential for catalytic activity (Dierks et al, 2005). Recent studies reported that human Sulfs (HSulfs) catalyzed the 6-O-desulfation of HS through an original, processive, and orientated mechanism (Seffouh et al, 2013), and that substrate recognition by the enzyme HD domain involved multiple, highly dynamic, non-conventional interactions (Harder et al, 2015;Walhorn et al, 2018).…”

Extracellular Endosulfatase Sulf-2 Harbours a Chondroitin/Dermatan Sulfate Chain That Modulates Its Enzyme Activity

“…Furin cleavage (Tang and Rosen, 2009) and N-glycosylations (Ambasta et al, 2007;Seffouh et al, 2019b) may be dispensable for the enzyme activity, but play a role in the enzyme attachment to the cell surface, while conversion of C88 into a FGly residue is a hallmark of all sulfatases and is essential for the catalytic activity (Dierks et al, 2005). Recent studies reported that human Sulfs (HSulfs) catalyzed the 6-O-desulfation of HS through an original, processive and orientated mechanism (Seffouh et al, 2013), and that substrate recognition by the enzyme HD domain involved multiple, highly dynamic, non-conventional interactions (Harder et al, 2015;Walhorn et al, 2018).…”