When you know that a particular chemical reaction occurs in biology (e.g. glucose -> glucose-6-phosphate in glycolysis) you can use this activity to guide the isolation of the enzyme that catalyzes that transformation. During enzyme purification the aim is to winnow away the thousands of contaminating proteins leaving just the one you want. Traditionally, great… Continue reading Putting the cart before the horse
The “bad actor” quote comes from a recent paper by Douglas Lake and collaborators: “Expression of Quiescin Sulfhydryl Oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in luminal B breast cancer” The enzyme: readers of earlier blogs may know that Quiescin-sulfhydryl oxidases (QSOXs) catalyze disulfide bond generation within… Continue reading QSOX as a “bad actor” in (some forms of) breast cancer
We have published a body of work on a small sulfhydryl oxidase – reasonably fundamental stuff I thought. We found new substrates, new enzymatic activities, explored enzymatic mechanisms and, with colleagues, solved crystal structures. So I was disconcerted that a speaker at a recent conference never mentioned any of our contributions in his talk on… Continue reading Conduct Unbecoming
What’s your favorite element? – for many scientists studying oxidative protein folding it would have to be sulfur. Not only does the oxidation of cysteinyl sulfur generate the constellation of structural disulfide bonds found in secreted proteins, but cysteine residues are an essential catalytic ingredient in the enzymes that form and isomerize these very disulfide… Continue reading Expanding the Biological NMR Toolbox
fishing for electrons with thioredoxin domains The QSOX family of disulfide bond-generating enzymes are ancient fusions of one or two thioredoxin domains linked to a helix-rich domain and then to an ERV domain. Algae, plants and protists have a single complete thioredoxin domain (blue bar) with a redox-active CxxC disulfide (Panel A). Metazoans contain an… Continue reading QSOX crystal structures
Shortness of breath (a.k.a. dyspn(o)ea) is caused by a wide range of conditions including acute anxiety, asthma, several lung diseases and infections, and various forms of heart failure. In a recent paper, Mebazaa et al. [PubMed] sought new serum markers that would specifically identify those patients whose labored breathing was due to heart failure. … Continue reading QSOX and the heart
A story of enzymological serendipity Our story of scientific serendipity starts in the early 1950’s, with a commercial poultry breeder in Williamsport, Pennsylvania, who noticed that several of his pedigree crosses laid eggs that did not hatch. The eggs were fertile – the embryos developed initially normally – but they died in the egg at… Continue reading Mutant Chickens in Pennsylvania
A “new” biomaterial from a surprising place “I think that, if required on pain of death to name instantly the most perfect thing in the universe, I would risk my fate on a bird’s egg.” (Thomas Wentworth Higginson; 1823-1911) So how does a chicken construct this paragon of perfection? Yolk is first, white… Continue reading The chicken and the egg