Janet Smith Uncovers Structure of Protein Involved in Vitamin B6 Biosynthesis
July 29, 2005
ANN ARBOR, Mich---LSI research professor Janet Smith has elucidated the structure of an enzyme involved in the biosynthesis of vitamin B6, one of the many vitamins essential in the human diet, in two chemical steps. Steps One and Two take place in small pockets in the protein called active sites. This study is part of a large project in Smith's group to understand enzymes that catalyze two-step chemical reactions. In other two-step enzymes, the two active sites are far apart so that the chemical product of Step One must travel through a tunnel in the enzyme to reach the active site for Step Two.
Dr. Smith's group crystallized the part of the vitamin B6 enzyme that carries out Step Two. The protein turns out to have a very familiar structure (the "beta/alpha barrel"), so familiar in fact, that the active site location is already mapped exactly. The remarkable thing about the structure is that 12 proteins come together in a beautiful symmetric cylinder - this arrangement is both unusual and unexpected. Additionally, the inside of the cylinder is hollow and the active sites all point into it.
"The $64,000 question is how the protein that catalyzes Step One delivers its product to those 12 active sites. We know that 12 of the Step One proteins bind to the big cylinder. Do the Step One proteins simply dump their product into the cylinder, or is a tunnel formed to each of the 12 active sites?" Smith said. "We're working on that question now."
No human genetic diseases are associated with this protein because humans don't make vitamin B6 - vitamins are essential chemicals that we cannot make and must eat. However, the enzyme is essential to plants, fungi and some bacteria, and therefore it may be possible to develop effective herbicides and antibiotics that block its active site.
Smith is the lead author in the cover story of the Journal of Biological Chemistry, "A new arrangement of (beta/alpha)8 barrels in the synthase subunit of PLP synthase" appearing in the July 29, 2005 issue.
The Life Sciences Institute serves as Michigan's hub for collaborative biomedical research on human health problems. Housed in a state-of-the-art building, the LSI is located between central campus and the medical complex in Ann Arbor.
