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Substrate-induced dimerization of elaiophylin glycosyltransferase reveals a novel self-activating form of glycosyltransferase for symmetric glycosylation
Acta Crystallographica Section D ( IF 2.6 ) Pub Date : 2022-09-27 , DOI: 10.1107/s2059798322008658 Tingting Xu 1 , Qingqing Gan 1 , Qiang Liu 1 , Ruidong Chen 2 , Xuhui Zhen 1 , Changsheng Zhang 2 , Jinsong Liu 1
Acta Crystallographica Section D ( IF 2.6 ) Pub Date : 2022-09-27 , DOI: 10.1107/s2059798322008658 Tingting Xu 1 , Qingqing Gan 1 , Qiang Liu 1 , Ruidong Chen 2 , Xuhui Zhen 1 , Changsheng Zhang 2 , Jinsong Liu 1
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Elaiophylin (Ela), a unique 16-membered symmetric macrodiolide antibiotic, displays broad biological activity. Two rare 2-deoxy-l-fucose moieties at the ends of Ela are critical for its activity. Previously, elaiophylin glycosyltransferase (ElaGT) was identified as the enzyme that is responsible for the symmetric glycosylation of Ela, acting as a potential enzymatic tool for enhancing the diversity and activity of Ela. However, a symmetric catalytic mechanism has never been reported for a glycosyltransferase (GT). To explore the catalytic mechanism, the structure of ElaGT was determined in four forms: the apo form and Ela-bound, thymidine diphosphate-bound and uridine diphosphate-bound forms. In the Ela-bound structure, two ElaGTs form a `face-to-face' C2-symmetric homodimer with a continuous acceptor-binding pocket, allowing a molecule of Ela to shuffle through. Interestingly, this dimer interface resembles that of the activator-dependent GT EryCIII with its activator EryCII. Sequence analysis also indicates that ElaGT belongs to the activator-dependent GT family, but no putative activator has been identified in the Ela gene cluster. It was then found that the ElaGT homodimer may utilize this `face-to-face' arrangement to stabilize the Ela-binding loops on the interface and to simultaneously allosterically regulate the catalytic center. Therefore, these structures present a novel self-activating model for symmetric sugar transfer in the GT family and a new potential regulation site for substrate specificity.
中文翻译：
底物诱导的油茶素糖基转移酶二聚化揭示了一种用于对称糖基化的新型自激活糖基转移酶形式
Elaiophylin (Ela) 是一种独特的 16 元对称大环二内酯抗生素，具有广泛的生物活性。Ela 末端的两个罕见的 2-脱氧-l-岩藻糖部分对其活性至关重要。此前，漆树碱糖基转移酶 (ElaGT) 被确定为负责 Ela 对称糖基化的酶，可作为增强 Ela 多样性和活性的潜在酶促工具。然而，从未报道过糖基转移酶（GT）的对称催化机制。为了探索催化机制，ElaGT 的结构被确定为四种形式：apo 形式和 Ela 结合形式、胸苷二磷酸结合形式和尿苷二磷酸结合形式。在 Ela-bound 结构中，两个 ElaGT 形成一个“面对面” C具有连续受体结合口袋的 2 对称同二聚体，允许 Ela 分子改组通过。有趣的是，这种二聚体界面类似于依赖于激活剂的 GT EryCIII 及其激活剂 EryCII。序列分析还表明 ElaGT 属于激活剂依赖性 GT 家族，但在 Ela 基因簇中没有发现推定的激活剂。然后发现 ElaGT 同源二聚体可以利用这种“面对面”排列来稳定界面上的 Ela 结合环并同时变构调节催化中心。因此，这些结构为 GT 家族中的对称糖转移提供了一种新的自激活模型，并为底物特异性提供了一个新的潜在调控位点。
更新日期：2022-09-27
中文翻译：
底物诱导的油茶素糖基转移酶二聚化揭示了一种用于对称糖基化的新型自激活糖基转移酶形式
Elaiophylin (Ela) 是一种独特的 16 元对称大环二内酯抗生素，具有广泛的生物活性。Ela 末端的两个罕见的 2-脱氧-l-岩藻糖部分对其活性至关重要。此前，漆树碱糖基转移酶 (ElaGT) 被确定为负责 Ela 对称糖基化的酶，可作为增强 Ela 多样性和活性的潜在酶促工具。然而，从未报道过糖基转移酶（GT）的对称催化机制。为了探索催化机制，ElaGT 的结构被确定为四种形式：apo 形式和 Ela 结合形式、胸苷二磷酸结合形式和尿苷二磷酸结合形式。在 Ela-bound 结构中，两个 ElaGT 形成一个“面对面” C具有连续受体结合口袋的 2 对称同二聚体，允许 Ela 分子改组通过。有趣的是，这种二聚体界面类似于依赖于激活剂的 GT EryCIII 及其激活剂 EryCII。序列分析还表明 ElaGT 属于激活剂依赖性 GT 家族，但在 Ela 基因簇中没有发现推定的激活剂。然后发现 ElaGT 同源二聚体可以利用这种“面对面”排列来稳定界面上的 Ela 结合环并同时变构调节催化中心。因此，这些结构为 GT 家族中的对称糖转移提供了一种新的自激活模型，并为底物特异性提供了一个新的潜在调控位点。
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