Structure of cytosine transport protein CodB provides insight into nucleobase-cation symporter 1 mechanism.
Structure of cytosine transport protein CodB provides insight into nucleobase-cation symporter 1 mechanism.
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DOI：
10.15252/embj.2021110527
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发表时间：
2022-08-16
期刊：
影响因子：
11.4
通讯作者：
Cameron, Alexander D.
中科院分区：
文献类型：
--
作者：
Hatton, Caitlin E.;Brotherton, Deborah H.;Spencer, Mahalah;Cameron, Alexander D.
CodB是来自核碱基-阳离子-共转运蛋白-1（NCS 1）转运蛋白家族的胞嘧啶转运蛋白，是广泛分布的LeuT超家族的成员。先前对医院病原体铜绿假单胞菌的实验表明，CodB对5-氟胞嘧啶的摄取也很重要，5-氟胞嘧啶被认为是一种通过抑制毒力来对抗抗菌素耐药性的新药。在这里，我们解决了从普通变形杆菌的CodB的晶体结构，在2.4 μ m的分辨率与胞嘧啶复合。我们表明，CodB进行胞嘧啶的钠依赖性摄取，并可以结合5-氟胞嘧啶。比较CodB和海因转运蛋白Mhp 1的底物结合结构，这是已知结构的唯一其他NCS 1家族成员，突出了底物与主链在不连续螺旋TM 6断点处形成氢键的重要性。与其他LeuT超家族成员相比，CodB和Mhp 1都不与TM 1上的残基发生特异性相互作用。结构的比较提供了深入了解这些蛋白质如何跨质膜运输底物的复杂机制。来自普通变形杆菌的药物摄取相关CodB与胞嘧啶复合物的晶体结构揭示了新的机制细节。
CodB is a cytosine transporter from the Nucleobase‐Cation‐Symport‐1 (NCS1) transporter family, a member of the widespread LeuT superfamily. Previous experiments with the nosocomial pathogen Pseudomonas aeruginosa have shown CodB as also important for the uptake of 5‐fluorocytosine, which has been suggested as a novel drug to combat antimicrobial resistance by suppressing virulence. Here we solve the crystal structure of CodB from Proteus vulgaris, at 2.4 Å resolution in complex with cytosine. We show that CodB carries out the sodium‐dependent uptake of cytosine and can bind 5‐fluorocytosine. Comparison of the substrate‐bound structures of CodB and the hydantoin transporter Mhp1, the only other NCS1 family member for which the structure is known, highlight the importance of the hydrogen bonds that the substrates make with the main chain at the breakpoint in the discontinuous helix, TM6. In contrast to other LeuT superfamily members, neither CodB nor Mhp1 makes specific interactions with residues on TM1. Comparison of the structures provides insight into the intricate mechanisms of how these proteins transport substrates across the plasma membrane. The crystal structure of drug uptake‐linked CodB from Proteus vulgaris in a complex with cytosine reveals new mechanistic details.
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影响因子：
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作者：
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DOI：
10.1107/s0907444904019158
发表时间：
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DOI：
10.1073/pnas.1222706110
发表时间：
2013-04-30
影响因子：
11.1
作者：
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