的晶体结构ADP-L-glycero-D-mannoheptose 6-epimerase:催化。
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执事,倪y,科尔曼WG Jr Ealick SE
的晶体结构ADP-L-glycero-D-mannoheptose 6-epimerase:催化。
结构。2000年5月15日,8 (5):453 - 62。
- PubMed ID
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10896473 (在PubMed]
- 文摘
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背景:ADP-L-glycero——mannoheptose 6-epimerase (AGME)所需的脂多糖(LPS)的生物合成在大多数属致病性和非致病性的革兰氏阴性细菌。它催化的互变现象ADP-D-glycero-D-mannoheptose ADP-L-glycero-D-mannoheptose, 7号碳糖的前体L-glycero-mannoheptose(庚糖)。庚糖是一个有限合伙人的义务组件核心领域;其缺失导致截断LPS结构导致抗生素对疏水性的易感性。庚糖不是哺乳动物细胞中,因此其在细菌的生物合成途径提供了一个独特的新型抗菌药物的设计目标。结果:AGME的结构,在复杂的辅酶ii和催化抑制剂ADP-glucose 2.0分辨率决定了多波长反常衍射(疯狂)分阶段方法。AGME homopentameric酶,结晶和两个五聚物的不对称单元。70年结晶学独立硒站点的位置结构确定过程中的关键步骤。每个单体包括两个领域:一个大的n端结构域,包括修改seven-stranded罗斯曼褶皱与辅酶ii绑定相关联;和一个较小的α/βc端域参与底物结合。 CONCLUSIONS: The first structure of an LPS core biosynthetic enzyme leads to an understanding of the mechanism of the conversion between ADP-D-glycero--mannoheptose and ADP-L-glycero-D-mannoheptose. On the basis of its high structural similarity to UDP-galactose epimerase and the three-dimensional positions of the conserved residues Ser116, Tyr140 and Lys144, AGME was classified as a member of the short-chain dehydrogenase/reductase (SDR) superfamily. This study should prove useful in the design of mechanistic and structure-based inhibitors of the AGME catalyzed reaction.