Similarities and Differences Between the Acyl-CoA Dehydrogenase and Acyl-CoA Oxidase Catalyzed Reactions: Kinetic and Structural-Functional Investigations

;​我不知道，我不知道，我不知道，我不知道，我不知道，我不知道，我不知道。哦，我要把我的头发剪掉，然后再剪掉。4 @ B E C D F G H I JF Microsoft Word 6.0文档MSWordDoc。6;​“存档文件夹”：“公告板”：“文件夹”：“留言”无法读取。消息内容来自：转发者：发送到邮件列表：请求接收到布告栏：抄送：抄送邮件列表：密件抄送：发送到文件夹：发送：主题：主题：未知收件人9507292 Srivastava将研究酰基辅酶a脱氢酶和酰基辅酶a氧化酶催化反应的异同。虽然这些酶看起来结构不同，但已知它们催化相同的化学转化反应，尽管在生理上利用不同类型的电子受体（即电子转移黄蛋白，ETF，与O2）。这些酶的整体催化机制有多相似和/或不同？P.I.将采用动力学和其他物理技术对这些酶进行比较机制和结构功能研究。(1)通过利用各种显色/显色底物/产物对，他们将确定在配体结合和/或催化过程中酶位点环境对这些物种电子结构的影响。他们将研究FAD和显色型烯丙辅酶a在酶烯丙辅酶a复合物内不同光谱变化的分子基础。(2)他们将研究这些底物和/或产物的键结构的变化是否与这些酶的蛋白质结构的变化直接相关。将确定蛋白质构象变化对配体结合和/或催化的影响程度。(3)他们将在各种实验条件下对这些酶的“还原”和“氧化”半反应进行详细的比较研究。将特别强调辨别酰基辅酶a氧化酶催化的“还原”半反应是否也涉及亚稳中间物质的形成？这些酶的氧化半反应的微观途径有何不同？(4) pH和氘同位素对这些酶的瞬态和稳态动力学特征的影响将被检查。在这些实验的基础上，推导了这些酶将酰基辅酶a转化为相应的烯基辅酶a的过渡态的性质。根据已知的中链脂肪酸酰基辅酶a脱氢酶的三维结构，并通过计算机图形模型构建研究，对这些研究得出的实验结果进行合理化。这是对酰基辅酶a脱氢酶和酰基辅酶a氧化酶催化反应的异同的研究。虽然这些酶看起来结构不同，但已知它们催化相同的化学转化反应，尽管在生理上利用不同类型的电子受体（即电子转移黄蛋白，ETF，相对于O2）。就其整体催化机制而言，这些酶有多相似和/或不同？这些酶的比较机制和结构功能研究将使用动力学和其他物理技术进行。从这些研究中得出的实验结果将根据已知的中链脂肪酸酰基辅酶A脱氢酶的三维结构和计算机图形模型构建研究进行合理化。*** *** *** *** *** *** *** *** *** *** *** *** *** *** *** *Oh +' 0 $ H l D H R:\WWUSER\TEMPLATE\NORMAL。DOT玛西娅·斯坦伯格朗达·杨@ u9 @ qp：@ j6 Microsoft Word 6.0E = E p ！pjjjjjjjj11。

; R o o t E n t r y F 'qRp: C o m p O b j b W o r d D o c u m e n t ! O b j e c t P o o l 'qRp: 'qRp: 4 @ A B C D E F G H I J F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; Esc to end Archive folder: Bulletin Board: Folder: Message cannot be read. Message Contents From: Forwarded by: To mailing list: Receipt Requested To bulletin board: cc: cc mailing list: bcc: To folder: To: Subject: Subject: Unknown recip9507292 Srivastava The similarities and differences between the acyl CoA dehydrogenase and acyl CoA oxidase catalyzed reactions will be studied. Although these enzymes appear to be structurally different, they are known to catalyze the same chemical transformation reaction, albeit by utilizing (physiologically) different types of electron acceptors (i.e., electron transferring flavoprotein, ETF, versus O2. How similar and/or different are these enzymes as regards to their overall catalytic mechanisms? The P.I. will to undertake a comparative mechanistic and structural functional studies of these enzymes by employing kinetic and other physical techniques. (1) By utilizing a variety of chromogenic/chromophoric substrate/product pairs, they will ascertain the influence of the enzyme site environments on the electronic structures of these species during the ligand binding and/or catalysis. They will examine the molecular basis of the diverse spectral changes of both FAD and chromophoric enoyl CoA's within the enzyme enoyl CoA complexes. (2) They will investigate whether the changes in the bond structure s of these substrates and/or products are directly coupled to the changes in the protein structures of these enzymes. The extent to which the protein conformational changes influence the ligand binding and/or catalysis will be ascertained. (3) They will undertake a detailed comparative investigation of the "reductive" and "oxidative" half reactions of these enzymes under a variety of experimental conditions. Particular emphasis will be made to discern whether the acyl CoA oxidase catalyzed "reductive" half reaction also involves formation of a metastable intermediary species? How different are the microscopic pathways of the oxidative half reactions of these enzymes? (4) The influence of pH and deuterium isotopes on the transient and steady state kinetic profiles of these enzymes will be examined. Based on these experiments, the nature of the transition states during the conversion of acyl CoA's to the corresponding enoyl CoA's by these enzymes will be deduced. The experimental results derived from these studies will be rationalized in the light of the known three dimensional structure of medium chain fatty acyl CoA dehydrogenase and by computer graphic model building studies. %%% This is an investigation of the similarity and differences between the acyl CoA dehydrogenase and acyl CoA oxidase catalyzed reactions. Although these enzymes appear to be structurally different, they are known to catalyze the same chemical transformation reaction, albeit by utilizing (physiologically) different types of electron acceptors (i.e., electron transferring flavoprotein, ETF, versus O2) How similar and/or different are these enzymes as regards to their overall catalytic mechanisms? A comparative mechanistic and structural-functional studies of these enzymes will be performed using kinetic and other physical techniques The experimental results derived from these studies will be rationalized in the light of the known three dimensional structure of medium chain fatty acyl CoA dehydrogenase and by the computer graphic model building studies. *** @ @ S u m m a r y I n f o r m a t i o n ( @ Oh +' 0 $ H l D h R:\WWUSER\TEMPLATE\NORMAL.DOT marcia steinberg Rhonda Young @ U 9 @ @ 'qRp: @ J 6 Microsoft Word 6.0 4 e = e p ! p j j j j j j j l 1 .