Serum albumin seen in three dimensions.

Serum albumin seen in three dimensions

Like one of those does-everything gadgets advertised on late-night television, serum albumin -- the most abundant blood protein -- plays more roles than would seem reasonable for a single molecule. It regulates blood volume. It stores molecules and shuttles some of them through the circulatory labyrinth. It also controls the blood concentration and bodily distribution of many drugs.

NASA researchers have determined the three-dimensional structure of human serum albumin with enough detail to visualize what parts of the protein bind aspirin, Valium, calcium and other molecules. Reporting in the June 9 SCIENCE, the scientists say their work should help researchers uncover molecular details responsible for the protein's versatility. It also could help drug designers circumvent serum albumin's tendency to mop drugs out of the bloodstream before the drugs can reach their targets.

"People have thought of serum albumin as being a sticky molecule," says crystallographer Daniel C. Carter, leader of the research team at the Marshall Space Flight Center in Huntsville, Ala. The crystal structure suggests that only a few regions of the cigar-shaped protein are responsible for this stickiness and that these areas bind chemically diverse molecules and atoms ranging from calcium to fatty acids to aspirin.

To determine a protein's structure using X-ray crystallography, researchers begin by growing millimeter-sized crystals that are stable and strong enough to withstand analysis, which involves bouncing X-rays off the crystal's features and noting the pattern and strength of reflected rays. No other group has grown serum albumin crystals hardy enough for such study, remarks British chemist Max F. Perutz of Cambridge University's Laboratory of Molecular Biology, winner of the 1962 Nobel prize in chemistry for solving the crystal structure of hemoglobin.

Using a battery of mathematical tools for making sense of data collected from hundreds of crystals, the NASA researchers discovered how human serum albumin's chain of 585 amino acids snakes around to form the protein's biologically active three-dimensional shape. Next, Carter expects to use an especially intense X-ray source to do even higher-resolution studies that could reveal the chemical mechanisms at work in albumin's sticky zones.

"When [Carter] has done this, it will be of immense help for drug design," Perutz told SCIENCE NEWS. One specific use might be for designing drugs to treat sickle cell anemia. Perutz says such drugs show promise in the test tube but cannot elude serum albumin's sticky grasp.