3-DIMENSIONAL STRUCTURE OF THE MUSCLE FATTY-ACID-BINDING PROTEIN ISOLATED FROM THE DESERT LOCUST SCHISTOCERCA-GREGARIA

The three-dimensional structure of the fatty-acid-binding protein isol ated from the flight muscle of the desert locust Schistocerca gregaria has been solved and refined to a crystallographic R-value of 18.5% fo r all measured X-ray data from 30.0- to 2.2-Angstrom resolution. Cryst als employed in the investigation were grown from 2.6 to 2.8 M ammoniu m sulfate solutions, buffered at pH 7.5 and containing 2-5% 2-methyl-2 .4-pentanediol. They belonged to the space group P2(1) with unit cell dimensions of alpha = 61.1 Angstrom, b = 44.8 Angstrom, c = 63.9 Angst rom, and beta = 113.6 degrees and two molecules per asymmetric unit. T he protein fold consists of ten strands of antiparallel beta-pleated s heet that wrap around to form a beta-barrel. In addition, there are tw o small alpha-helices and six type I, two type II, and two type II' tu rns. The two molecules pack in the asymmetric unit as a dimer with a l ocal 2-fold rotational axis. The subunit-subunit interface involves am ino acid side chains located in the area of the helix-turn-helix motif and the turn between beta-strands E and F. It is this area that has b een speculated to form the portal through which fatty acids enter the binding cavity. There are 23 solvent molecules that are conserved betw een the two independent molecules in the asymmetric unit. Nine of thes e waters play important structural roles. A three-dimensional comparis on between the insect and human muscle fatty-acid-binding proteins sho ws that their alpha-carbons superimpose with a root-mean-square deviat ion of 0.77 Angstrom for 89 structurally equivalent atoms. This high t ertiary homology between these two proteins is surprising in light of the fact that they developed independently for more than 500 million y ears.