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

酰基辅酶A脱氢酶和酰基辅酶A氧化酶催化反应的异同：动力学和结构功能研究

• 批准号: 9507292
• 负责人: D. Srivastava
• 金额: $ 24万
• 依托单位: North Dakota State University Fargo
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9507292&HistoricalAwards=false
• 关键词: Similarities; Differences; Between; Acyl; CoA

; 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 .