Human thymidylate synthase (hTS) is a 72 kDa homodimeric enzyme responsible for the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), making it the sole source of de novo dTMP in human cells. As a result, hTS is an attractive anti-cancer therapeutic target. Additionally, hTS is known to possess a number of interesting biophysical features, including adoption of active and inactive conformations, positively cooperative substrate binding, half-the-sites activity, and interacting with its own mRNA. The physical mechanisms underlying these properties, and how they may be leveraged to guide therapeutic development, are yet to be fully explored. Here, as a preface to detailed NMR characterization, we present backbone amide and ILVM methyl resonance assignments for hTS in apo and dUMP bound forms. In addition, we present backbone amide resonance assignments for hTS bound to a substrate analog and the native cofactor.

人胸苷酸合酶 (hTS) 是一种 72 kDa 同二聚酶，负责将脱氧尿苷单磷酸 (dUMP) 转化为脱氧胸苷单磷酸 (dTMP)，使其成为人类细胞中从头 dTMP 的唯一来源。因此，hTS 是一个有吸引力的抗癌治疗靶点。此外，已知 hTS 具有许多有趣的生物物理特征，包括采用活性和非活性构象、积极协同底物结合、半位点活性以及与其自身 mRNA 相互作用。这些特性背后的物理机制，以及如何利用它们来指导治疗开发，尚未得到充分探索。在这里，作为详细 NMR 表征的前言，我们提出了 apo 和 dUMP 结合形式的 hTS 的主链酰胺和 ILVM 甲基共振归属。此外，我们还提出了与底物类似物和天然辅因子结合的 hTS 的骨架酰胺共振分配。