细菌甲硫氨酸氨肽酶抑制作用的研究进展
Advances in Bacterial Methionine Aminopeptidase Inhibition.
作者信息
Helgren Travis R, Wangtrakuldee Phumvadee, Staker Bart L, Hagen Timothy J
机构信息
Northern Illinois University, Department of Chemistry and Biochemistry, DeKalb, IL 60115 USA.
出版信息
Curr Top Med Chem. 2016;16(4):397-414. doi: 10.2174/1568026615666150813145410.
Methionine aminopeptidases (MetAPs) are metalloenzymes that cleave the N-terminal methionine from newly synthesized peptides and proteins. These MetAP enzymes are present in bacteria, and knockout experiments have shown that MetAP activity is essential for cell life, suggesting that MetAPs are good antibacterial drug targets. MetAP enzymes are also present in the human host and selectivity is essential. There have been significant structural biology efforts and over 65 protein crystal structures of bacterial MetAPs are deposited into the PDB. This review highlights the available crystallographic data for bacterial MetAPs. Structural comparison of bacterial MetAPs with human MetAPs highlights differences that can lead to selectivity. In addition, this review includes the chemical diversity of molecules that bind and inhibit the bacterial MetAP enzymes. Analysis of the structural biology and chemical space of known bacterial MetAP inhibitors leads to a greater understanding of this antibacterial target and the likely development of potential antibacterial agents.
甲硫氨酸氨肽酶（MetAPs）是一种金属酶，可从新合成的肽和蛋白质中切割掉N端甲硫氨酸。这些MetAP酶存在于细菌中，基因敲除实验表明，MetAP活性对细胞生命至关重要，这表明MetAPs是良好的抗菌药物靶点。MetAP酶也存在于人类宿主中，选择性至关重要。结构生物学领域已经付出了巨大努力，超过65个细菌MetAPs的蛋白质晶体结构已存入蛋白质数据银行（PDB）。本综述重点介绍了细菌MetAPs的现有晶体学数据。细菌MetAPs与人类MetAPs的结构比较突出了可能导致选择性的差异。此外，本综述还包括结合并抑制细菌MetAP酶的分子的化学多样性。对已知细菌MetAP抑制剂的结构生物学和化学空间进行分析，有助于更深入地了解这一抗菌靶点以及潜在抗菌剂的可能开发情况。
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