Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis.
Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis.
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DOI：
10.1107/s2053230x21013078
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发表时间：
2022-01-01
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影响因子：
--
通讯作者：
Asojo OA
中科院分区：
文献类型：
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作者：
Porter I;Neal T;Walker Z;Hayes D;Fowler K;Billups N;Rhoades A;Smith C;Smith K;Staker BL;Dranow DM;Mayclin SJ;Subramanian S;Edwards TE;Myler PJ;Asojo OA
FolM替代二氢叶酸还原酶1的晶体结构从猪布鲁氏菌和犬布鲁氏菌揭示原型NADPH依赖性短链还原酶的结构相似的原生动物蝶啶还原酶，是潜在的药物靶点。布鲁氏菌属细菌的成员引起布鲁氏菌病，这是一种影响牲畜和野生动物的人畜共患疾病。布鲁氏杆菌属B类传染性病原体，可雾化用于生物战。作为西雅图传染病结构基因组学中心（SSGCID）的结构基因组学研究的一部分，产生了来自猪布鲁氏菌和犬布鲁氏菌的FolM替代二氢叶酸还原酶1，并报道了它们的结构。这些酶共享约95%的序列同一性，但与具有已知结构的其他同源物具有小于33%的序列同一性。这些结构是原型NADPH依赖性短链还原酶，与原生动物蝶啶还原酶具有最高的三级结构相似性，目前正在研究合理的治疗开发。
Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis reveal prototypical NADPH-dependent short-chain reductases with structural similarity to protozoan pteridine reductases that are potential drug targets. Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that can be aerosolized for biological warfare. As part of the structural genomics studies at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), FolM alternative dihydrofolate reductases 1 from Brucella suis and Brucella canis were produced and their structures are reported. The enzymes share ∼95% sequence identity but have less than 33% sequence identity to other homologues with known structure. The structures are prototypical NADPH-dependent short-chain reductases that share their highest tertiary-structural similarity with protozoan pteridine reductases, which are being investigated for rational therapeutic development.