The crystal structure of Escherchia coli asparaginase II (EC 3.5.1.1), a drug (Elspar) used for the treatment of acute lymphoblastic leukemia, has been determined at 2.3 A resolution by using data from a single heavy atom derivative in combination with molecular replacement. The atomic model was refined to an R factor of 0.143. This enzyme, active as a homotetramer with 222 symmetry, belongs to the class of a/P proteins. Each subunit has two domains with unique topological features. On the basis of present structural evidence consistent with previous biochemical studies, we propose locations for the active sites between the N-and C-terminal domains belonging to different subunits and postulate a catalytic role for Thr-89.

T cell receptor (TCR) binding degeneracy lies at the heart of several physiological and pathological phenomena, yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and an octapeptide (VSV8) bound to the H-2K(b) major histocompatibility complex molecule at a 2.7 A resolution, and compared it with the BM3.3 TCR bound to the H-2K(b) molecule loaded with a peptide that has no primary sequence identity with VSV8. Comparison of these structures showed that the BM3.3 TCR complementarity-determining region (CDR) 3alpha could undergo rearrangements to adapt to structurally different peptide residues. Therefore, CDR3 loop flexibility helps explain TCR binding cross-reactivity.