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Menaquinone Physiochemical Properties Alter Energy Metabolism in Actinobacteria

甲基萘醌的理化性质改变放线菌的能量代谢

基本信息

批准号：
1709564
负责人：
Debbie Crans
金额：
$ 48万
依托单位：
Colorado State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2021-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709564&HistoricalAwards=false
关键词：
Menaquinone Physiochemical Properties Alter Energy

项目摘要

The Chemistry of Life Processes Program in the Chemistry Division funds this award. Professors Debbie Crans and Dean Crick from Colorado State University investigate how a specific molecule plays a crucial part in the generation of energy from nutrients (metabolic energy) in microorganisms. The first step in production of metabolic energy is electron transport- where electrons are passed stepwise through a series of small molecules and proteins embedded in a membrane. One of these molecules is menaquinone. It has been known for a long time that menaquinone is involved in the electron transport steps, but how it participates in the process is still unknown. The structure and reactivity of the menaquinone molecule is investigated in this research. The critical electron transfer reaction is exquisitely sensitive to the structure of menaquinone. The basis for this sensitivity is examined by making small variations in the shape of the molecule and measuring the effects on the metabolic energy generation. These studies allow undergraduate students, graduate students and postdoctoral fellows to acquire specialized training in synthesis, analysis of molecular structures in solution and at the interfaces of artificial membranes, and microbiological methodology. The topic is presented to the public in suitable settings including outreach programs with K-12 students and other community groups.The enzyme MenJ (Rv0561c) of Mycobacterium tuberculosis catalyzes the reductive conversion of menaquinone with nine isoprene units (MK-9) to menaquinone with nine isoprene units with the second isoprene unit saturated (MK-9(II-H2)). A subtle variation in the structure of MK-9(II-H2) results in surprisingly dramatic changes in survival and energy metabolism for the organism. How the conversion of a single bond to a double bond (MK-9(II-H2) to MK-9) could have such profound effects on the energy metabolism of mycobacteria is not understood. The current research project seeks to define the biological role of regiospecific saturation in MK derivatives. The physical properties of simple synthetic MK derivatives are investigated with the objective of elucidating the effects of saturation on solution structure, redox potentials, and molecular interactions at water/lipid interfaces. The results from these studies are used to develop an understanding for how these changes can affect MK's biological activities. The current hypothesis is that the shape of the molecule directs the biological responses.

该奖项由化学系生命过程化学项目资助。来自科罗拉多州立大学的Debbie Crans和Dean Crick教授研究了一种特定的分子如何在微生物从营养物质产生能量（代谢能）的过程中发挥关键作用。代谢能量产生的第一步是电子传递-电子逐步通过一系列嵌入膜中的小分子和蛋白质。其中一种分子是甲基萘醌。长期以来，人们已经知道甲基萘醌参与电子传递步骤，但它如何参与这一过程仍然是未知的。本研究对甲基萘醌分子的结构和反应活性进行了研究。临界电子转移反应对甲萘醌的结构非常敏感。这种灵敏度的基础是通过在分子的形状上进行微小的变化并测量对代谢能量产生的影响来检查的。这些研究使本科生，研究生和博士后研究员获得合成，在溶液中的分子结构分析和人工膜的界面，和微生物学方法的专门培训。结核分枝杆菌的酶MenJ（Rv 0561 c）催化具有9个异戊二烯单元的甲基萘醌（MK-9）还原转化为具有9个异戊二烯单元且第二个异戊二烯单元饱和的甲基萘醌（MK-9（II-H2））。MK-9（II-H2）结构的细微变化导致生物体的生存和能量代谢发生惊人的变化。单键转化为双键（MK-9（II-H2）转化为MK-9）如何对分枝杆菌的能量代谢产生如此深远的影响尚不清楚。目前的研究项目旨在确定MK衍生物中区域特异性饱和的生物学作用。简单的合成MK衍生物的物理性质进行了研究，目的是阐明饱和度对溶液结构，氧化还原电位和水/脂质界面的分子相互作用的影响。这些研究的结果用于了解这些变化如何影响MK的生物活性。目前的假设是，分子的形状指导生物反应。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Investigating Substrate Analogues for Mycobacterial MenJ: Truncated and Partially Saturated Menaquinones

DOI：
10.1021/acs.biochem.9b00007
发表时间：
2019-03-26
期刊：
BIOCHEMISTRY
影响因子：
2.9
作者：
Koehn, Jordan T.;Beuning, Cheryle N.;Crans, Debbie C.
通讯作者：
Crans, Debbie C.

Interactions of Truncated Menaquinones in Lipid Monolayers and Bilayers.

DOI：
10.3390/ijms22189755
发表时间：
2021-09-09
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Van Cleave C;Koehn JT;Pereira CS;Haase AA;Peters BJ;Croslow SW;McLaughlin KG;Werst KR;Goach AL;Crick DC;Arantes GM;Crans DC
通讯作者：
Crans DC

Effects of vanadium(IV) compounds on plasma membrane lipids lead to G protein-coupled receptor signal transduction