Redefining Renalase

肾酶是一种生物学功能未知的酶。 虽然它被描述为一种新的肾脏激素，由肾脏分泌到血液中，消耗肾上腺素，从而降低血压和减慢心率，但从未有过令人信服的证据证明这种活动。根据首席研究员最近的发现，似乎真正的功能与血压无关。 相反，肾酶似乎是一种补救酶，可以防止所有生物体中代谢核心分子的丢失。 这种分子倾向于改变其结构，使其在新陈代谢中无用。 肾酶通过将非活性分子转变为正确的活性结构，防止非活性分子的分解，从而挽救或挽救它们。 肾酶的这种功能涉及到前所未有的酶化学，很可能被发现是普遍存在的，被许多（如果不是所有）生命形式所利用。这个奖项的目的是建立一个基本的了解这种好奇的新的化学活动。 肾酶作为一种新兴的酶化学，将为研究生提供一个良好的教学平台。此外，首席研究员将把这项活动的新例子的发现融入到生物化学实验室的介绍课程中，这样本科生就可以通过在实验室课堂上做出真正的科学发现来直接参与这项研究的推进。Moran博士对一种新发现的酶--肾酶进行了描述，这种酶似乎对生物体的有效代谢活动很重要。该奖项将资助一系列研究活动，这些活动将定义肾酶的化学机制，活性的结构基础以及该活性的代谢重要性。所采用的方法将使用快速混合预稳态分光光度动力学技术，底物类似物和产物酶复合物的结构阐明，许多生物物理方法，利用酶的辅因子的分光光度报告能力和保守的活性位点氨基酸的定点诱变的组合。此外，莫兰打算开发一个本科实验室课程，让学生在广泛的生物体中发现这种化学的新例子，从而使该课程将提供新的调查途径，通过这些途径可以建立这种活动的全部重要性和背景。

Renalase was an enzyme of unknown biological function for almost a decade. While it was described as a new renal hormone secreted into blood by the kidney to consume adrenaline and thereby lower blood pressure and slow the heart rate, no convincing demonstration of this activity was ever made. Based on a recent discovery by the principal investigator, it appears that the true function has nothing to do with blood pressure. Renalase instead appears to be a salvage enzyme that prevents the loss of a molecule at the heart of metabolism in all living organisms. This molecule has a tendency to alter its structure in a way that makes it useless in metabolism. Renalase prevents the accumualtion of the inactive molecules, saving or salvaging them, by turning them back into the correct, active structure. This function for renalase involves unprecedented enzyme chemistry that is likely to be found to be pervasive, utilized by many if not all forms of life. The intent of this award is to establish a foundational understanding of this curious new chemical activity. As new enzyme chemistry, the investigation of renalase will be an excellent platform to teach graduate students about enzymology. Moreover, the principal investigator will integrate the discovery of new examples of this activity into an Introductory Biochemistry Laboratory class such that undergraduates can participate directly in the advancement of this research by making genuine scientific discoveries in the laboratory classroom.This award from the National Science Foundation, Division of Chemistry, Chemistry of Life Processes Program is funding Dr. Graham R. Moran from the University of Wisconsin-Milwaukee to characterize a newly discovered enzyme, renalase that would appear to be important for efficient metabolic activity in living organisms. The award will fund a range of research activities that will define the chemical mechanism of renalase, the structural basis for the activity, and the metabolic importance of this activity. The methods employed will use a combination of rapid-mixing pre-steady state spectrophotometric kinetic techniques, structural elucidation of substrate analog and product enzyme complexes, numerous biophysical approaches that take advantage of the spectrophotometric reporting power of the enzyme's cofactor and site directed mutagenesis of conserved active site amino acids. In addition, Dr. Moran intends to develop an undergradaute laboratory course in which students discover new examples of this chemistry in a broad range of organisms such that the course will provide new avenues of investigation by which the full importance of and context for this activity can be established.