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Structure Of Human Thymidylate Synthase Under Low-Salt Conditions, Leslie L. Lovelace, Wladek Minor, Lukasz Lebioda
Structure Of Human Thymidylate Synthase Under Low-Salt Conditions, Leslie L. Lovelace, Wladek Minor, Lukasz Lebioda
Faculty Publications
Human thymidylate synthase, a target in cancer chemotherapy, was crystallized from PEG 3350 with 30 mM ammonium sulfate (AS) in the crystallization medium. The crystals are isomorphous with the high-salt crystals (~2.0 M AS) and the structure has been solved and refined (R = 22.6%, Rfree = 24.3%) at 1.8 Å resolution. The high- and low-AS-concentration structures are quite similar, with loop 181-197 is in the inactive conformation. Also, residues 95-106 and 129-135 (eukaryotic inserts region) show high mobility as assessed by poor electron density and high values of crystallographic temperature factors (residues 1-25 and 108-129 are disordered in both …