Paul Sigler (1934–2000)

came in 1985 when he, Andrej Joachimiak, and others Paul Sigler, who died in January of a cardiac arrest while published the structure of the dimeric trp repressor of walking to work, embarked on protein crystallography E. coli. Comparisons of the structures of the repressor only two years after the first two structures had been with and without tryptophan and of the tryptophansolved, when it was a virgin field and an adventure, and bound repressor with the operator DNA revealed how he left it as one of its world leaders. Tall, outgoing, comcombination with tryptophan clamps the two reading panionable, voluble, generous, warm-hearted, compasheads of the repressor at the correct spacing to combine sionate, hospitable, irascible and good-natured, he was a with the palindromic bases in two successive major walking, running, talking human dynamo altogether larger groves of the double-helical operator DNA. The surpristhan life. He complained to me once that nowadays his ing finding that several of the links between the represpostdocs were not working as hard as he used to, but sor and the bases were water-mediated hydrogen bonds few of us did, even in those heroic days when we had raised many eyebrows, but a beautiful high-resolution no automatic diffractometers to measure the intensities structure of the repressor–operator complex laid these of our X-ray reflections. doubts to rest. Paul Sigler was born in Richmond, Virginia, the son These structures solved the stereochemical mechaof a chemist who worked there for Dupont. When he nism of the regulation of gene expression first proposed was five, Dupont transferred his father to Buffalo, NY, by Monod and Jacob in their classic paper in 1961. Its where Paul grew up. His proficiency in football gave wide interest led to Sigler’s appointment to the Chair him entry to Princeton, but there he found himself more at Yale, which he occupied until his death. This move talented in chemistry. After majoring in that subject, he initiated the most productive period of his life. He folenrolled in medicine at Columbia-Presbyterian where he lowed the trp repressor with several more protein–DNA obtained his M.D. and served as an intern and resident. complexes. The most spectacular one was the yeast Finding himself more attracted by research than by medTATA-binding protein bound to the TATA box; it revealed ical practice, he joined the National Institutes of Health an astonishing mechanism of recognition: phenylalanine in Bethesda, MD. side chains intercalating between bases open up the