Our group, in collaboration with Donald Coppock, uncovered a new enzyme family (abbreviated QSOX: Quiescin-sulfhydryl oxidase) that is capable of facile and direct  insertion of disulfide bonds into reduced unfolded client proteins.  Mispaired disulfide bonds are corrected by isomerization using a second enzyme, protein disulfide isomerase (PDI). QSOX enzymes are present in most eukaryotes, but… Continue reading →

Human augmenter of liver regeneration (ALR, a.k.a. hepatopoietin, HSS, GFER) is the most enigmatic of those sulfhydryl oxidases that show homology with the flavin binding domain of QSOX.  Early studies showed that damaged liver releases a circulatory growth factor eventually found to be a small flavin-linked sulfhydryl oxidase.  ALR is found both extracellularly and intracellularly. … Continue reading →

We are continuing our efforts to recapitulate oxidative protein folding in vitro:  in particular by developing efficient systems for folding proteins with complex disulfide connectivities.  The insights gained should help inform current debate concerning the way disulfide bonds are generated in the endoplasmic reticulum of higher eukaryotes. We have found that riboflavin binding protein (RfBP)… Continue reading →

Studies aimed towards the generation of inhibitors directed towards QSOX, and other enzymes with CxxC motifs, have led to the unexpected observation that arsenic(III) species can interfere with protein folding pathways by sequestration of reduced unfolded proteins.  This binding is dependent on the arsenic species and on the concentration of competing reduced glutathione.  Binding is… Continue reading →

Disulfide-rich structural proteins that are assembled into matrices, fibers, and envelopes are important in a wide range of biological settings – from the keratin-associated protein matrices in differentiating keratinocytes, to disulfide-rich structures formed during spermatogenesis.  We are currently studying a disulfide-rich biomaterial that is both commonplace and cryptic.  Under the shell of a chicken egg… Continue reading →