A putative open reading frame encoding GTP cyclohydrolase I from Listeria monocytogenes was expressed in a recombinant Escherichia coli strain. The recombinant protein was purified and was confirmed to convert GTP to dihydroneopterin triphosphate (Km = 53 µM; vmax = 180 nmol mg-1 min-1). The protein was crystallized from 1.3 M sodium citrate pH 7.3 and the crystal structure was solved at a resolution of 2.4 Å (Rfree = 0.226) by molecular replacement using human GTP cyclohydrolase I as a template. The protein is a D5-symmetric decamer with ten topologically equivalent active sites. Screening a small library of about 9000 compounds afforded several inhibitors with IC50 values in the low-micromolar range. Several inhibitors had significant selectivity with regard to human GTP cyclohydrolase I. Hence, GTP cyclohydrolase I may be a potential target for novel drugs directed at microbial infections, including listeriosis, a rare disease with high mortality.

中文翻译：

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单核细胞增生李斯特菌的 GTP 环水解酶 I 的结构，是一个潜在的抗感染药物靶点。


编码来自单核细胞增生李斯特氏菌的 GTP 环化水解酶 I 的推定开放阅读框在重组大肠杆菌菌株中表达。重组蛋白经过纯化并被证实可将 GTP 转化为二氢新蝶呤三磷酸（Km = 53 µM；vmax = 180 nmol mg-1 min-1）。该蛋白质从 1.3 M 柠檬酸钠 pH 7.3 中结晶，并使用人 GTP 环化水解酶 I 作为模板，通过分子置换以 2.4 Å (Rfree = 0.226) 的分辨率解析晶体结构。该蛋白是一种 D5 对称十聚体，具有 10 个拓扑等效的活性位点。筛选约 9000 种化合物的小型文库提供了几种 IC50 值在低微摩尔范围内的抑制剂。几种抑制剂对人 GTP 环化水解酶 I 具有显着的选择性。因此，GTP 环化水解酶 I 可能是针对微生物感染（包括李斯特菌病）这种罕见的高死亡率疾病的新药的潜在靶点。