Bolla Jani Reddy, Su Chih-Chia, Delmar Jared A, Radhakrishnan Abhijith, Kumar Nitin, Chou Tsung-Han, Long Feng, Rajashankar Kanagalaghatta R, Yu Edward W
Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA.
Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011, USA.
Nat Commun. 2015 Apr 20;6:6874. doi: 10.1038/ncomms7874.
The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.
叶酸生物合成途径作为抗生素开发靶点的潜力已得到临床验证。然而，许多病原体已对这些抗生素产生耐药性，促使人们重新评估该途径内潜在的药物靶点。嗜油栖热袍菌（Alcanivorax borkumensis）的ydaH基因编码AbgT家族转运蛋白的一种整合膜蛋白，此前尚无关于其结构的信息。在此，我们报道了嗜油栖热袍菌YdaH的晶体结构，揭示了一种二聚体分子，其结构不同于其他转运蛋白家族。YdaH是一个碗状二聚体，有一个从细胞质延伸至膜双层中部的充满溶剂的腔。该转运蛋白的每个亚基包含九个跨膜螺旋和两个发夹结构，这表明了底物转运的一种可能途径。进一步分析还表明，YdaH可能作为一种抗生素外排泵，并介导细菌对磺胺类抗代谢药物的耐药性。
