MUROPEPTIDE RECYCLING PATHWAY & BETA LACTAMASE INDUCTION

胞肽回收途径

• 批准号: 6519602
• 负责人: JAMES T PARK
• 金额: $ 6.66万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6519602
• 关键词: Escherichia coli; N acetylglucosaminidase; X ray crystallography; bacterial proteins; beta lactamase; biological signal transduction; cell wall; chemical binding; enzyme biosynthesis; enzyme induction /repression; enzyme structure; enzyme substrate; intracellular transport; microorganism metabolism; permease; protein transport

Uptake of cell wall degradation products via the muropeptide recycling pathway is required for induction of beta-lactamase. The MppA permease pathway for import of free murein tripeptide affects multidrug resistance so that a full understanding of these pathways has important implications for health. The broad, long-term objective of this research is to characterize the murein tripeptide recycling pathway and the Mpp permease, a new periplasmic binding-protein dependent permease pathway specific for murein tripeptide. We hypothesize that both the recycling pathway and the Mpp permease pathway have a monitoring function to signal changes in the condition of the cell wall so that the cell can respond to the changes appropriately. In addition to exploring these hypotheses, the proposed research will extend our understanding of the recycling pathway by characterizing the AmpG permease and the NagZ beta-N-acetylglucosaminidase and of the MppA permease pathway by determining its specificity and that of MppA itself. Specific aims: Aim 1: a. To determine the substrate specificity of AmpG permease, a permease required for murein recycling and beta-lactamase induction. b. To determine if NagZ beta-N-acetylglucosaminidase is needed to form the inducer for beta-lactamase and to determine the substrate specificity of NagZ. Aim 2: To determine if the recycling pathway is involved in signaling to the cell that its cell wall is being damaged. Aim 3: To determine the binding specificity of MppA and its binding constants for the murein tripeptide, L- Ala-gamma-D-Glu-meso-Dap and other tripeptides whose importation is facilitated by MppA. Aim 4: To determine if MppA is involved in signaling which is strongly suggested by several observations described in the progress report. Aim 5: To determine the crystal structure of MppA. Aim 6: To determine if groESL is required for export of MppA and OppA to the periplasm.

诱导β-内酰胺酶需要对细胞壁降解产物的吸收。 MPPA渗透性途径的途径导入游离Murein三肽会影响多药耐药性，因此对这些途径的全面了解对健康具有重要意义。 这项研究的广泛，长期的目标是表征Murein三肽回收途径和MPP Persease，这是一种针对Murein Thimeptide特异的新型周质结合蛋白依赖性蛋白质粘酶途径。 我们假设回收途径和MPP渗透率途径都具有监视功能，可以在细胞壁的状况中发出信号变化，以便细胞可以适当地响应变化。 除了探索这些假设外，拟议的研究还将通过表征AMPG验证酶和NAGZβ-N-乙酰基葡萄糖胺酶以及MPPA验证途径来确定其特异性和MPPA本身的MMPPA渗透途径，从而扩展我们对回收途径的理解。具体目的：目标1：为了确定AMPG渗透酶的底物特异性，Murein回收和β-内酰胺酶诱导所需的渗透酶。 b。为了确定是否需要NAGZβ-N-乙酰葡萄糖氨基酶来形成β-内酰胺酶的诱导剂并确定Nagz的底物特异性。 目标2：确定回收途径是否涉及向细胞发出损坏的细胞壁的信号。 AIM 3：确定MPPA及其结合常数的结合特异性，对MUREIN三肽，L- Ala-Gamma-D-Glu-Meso-DAP和其他由MPPA促进的三肽。 目标4：确定MPPA是否参与信号传导，这是由进度报告中描述的几个观察结果强烈建议。 目标5：确定MPPA的晶体结构。 目标6：确定是否需要Groesl出口MPPA和OPPA对周期。