Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, PA, Brasil.
Chem Biol Drug Des. 2017 Apr;89(4):599-607. doi: 10.1111/cbdd.12882. Epub 2016 Nov 16.
UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is one of the key enzymes involved in peptidoglycan biosynthesis. The peptide HESFWYLPHQSY (called PEP 1354) is an inhibitor of MurA with an IC value of 200 μm. In this article, we have used the FlexPepDock ab-initio protocol from the Rosetta program homology modeling and molecular dynamics simulations to analyze, for the first time, the interaction of the PEP 1354 peptide with MurA enzyme from Pseudomonas aeruginosa (MurA-PA). Our modeling results suggest that the peptide binds to the same active site as the natural substrate UDP-N-acetylglucosamine (UNAG). Additionally, the MurA-peptide complex revealed that the peptide seems to prevent the closure of the Pro114-123 loop and, consequently, the open-closed transition of the MurA structure.
尿苷二磷酸-N-乙酰葡萄糖胺烯醇式丙酮酸基转移酶（MurA）是参与肽聚糖生物合成的关键酶之一。肽 HESFWYLPHQSY（称为 PEP 1354）是 MurA 的抑制剂，其 IC 值为 200 μm。在本文中，我们首次使用 Rosetta 程序同源建模和分子动力学模拟中的 FlexPepDock ab-initio 协议来分析 PEP 1354 肽与铜绿假单胞菌（MurA-PA）的 MurA 酶的相互作用。我们的建模结果表明，该肽与天然底物尿苷二磷酸-N-乙酰葡萄糖胺（UNAG）结合在相同的活性位点上。此外，MurA-肽复合物表明，该肽似乎阻止了 Pro114-123 环的闭合，从而阻止了 MurA 结构的开-闭转变。
