W0397

Putative Functional Assignment of Yeast Hypothetical Protein YMR087W. D. Kumaran, S. Eswaramoorthy, F.W. Studier & S. Swaminathan, Biology Dept., Brookhaven National Laboratory, Upton, NY 11973.

Two of the major goals of the Structural Genomics Project are to catalog all possible protein folds and to understand the structure – function relationships of the proteins generated by the Human Genome. Yeast hypothetical protein YMR087W (hereafter P089) was chosen as one of the targets since it has a human homolog. It also has no significant sequence similarity to any of the proteins of known structures and its function is unknown. The structure of P089 has been determined by two-wavelength MAD phasing using selenomet protein. The structure has been refined with CNS to an R-value of 0.20 (R-free = 0.22) for data extending to 1.9 Å resolution. The molecule comprises two domains (N- and C-terminal) linked by a short loop. The N-terminal domain folds into a three layers αβα sandwich, though with a unique topology. The central β-sheet consists of six strands and is flanked by three helices on one side and two on the other. The C-terminal domain comprises a four helical bundle. In the crystal structure, P089 exists as a dimer through a crystallographic two-fold axis. Crystal structures of this protein with a few of its putative substrates have also been determined. The implication of these results on its function will be discussed.