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绵马鳞毛蕨的L-甲硫氨酸脱羧酶:纯化、特性、底物特异性、辅酶的无效转氨作用以及底物脱羧和辅酶转氨的立体化学过程

L-methionine decarboxylase from Dryopteris filix-mas: purification, characterization, substrate specificity, abortive transamination of the coenzyme, and stereochemical courses of substrate decarboxylation and coenzyme transamination.

作者信息

Stevenson D E, Akhtar M, Gani D

机构信息

Department of Chemistry, University of Southampton, U.K.

出版信息

Biochemistry. 1990 Aug 21;29(33):7631-47. doi: 10.1021/bi00485a013.

Abstract

L-Methionine decarboxylase from the male fern Dryopteris filix-mas has been purified 256-fold from acetone powder extracts to very near homogeneity. The enzyme is membrane-associated and requires detergent for solubilization during the initial extraction. The enzyme is a homodimer of subunit Mr 57,000 and shows a pH optimum at approximately 5.0 with 20 mM (2S)-methionine as substrate. The specific activity, kcat, for methionine is approximately 50 mol s(-1) (mol of active site)(-1) at pH 4.5 and below. A wide range of straight- and branched-chain (2S)-alkylamino acids are substrates for the enzyme. The values for the rate of decarboxylation, Vmax, and for the apparent Michaelis constant, Km, however, vary with structure and with the chirality at C-3. The pH dependence of V and V/K has been examined for three substrates: (2S)-methionine, valine, and leucine. Pyridoxal 5'-phosphate (PLP) is required for activity, and in the absence of excess PLP, the activity of the enzyme in incubations reduced with respect to time. The addition of PLP fully restores the activity, indicating that an abortive decarboxylation-transamination accompanies the normal decarboxylation reaction. The occurrence of the abortive reaction was confirmed by showing that [35S]methionine is converted to labeled 3-(methylthio)propionaldehyde while [4'-3H]PLP is converted to labeled pyridoxamine 5'-phosphate (PMP). The decarboxylation of (2S)-methionine gave 3-(methylthio)-1-aminopropane. Preparation of the N-camphanamide derivative of the amine allowed the C-1 methylene protons to be distinguished by 1H NMR spectroscopy. Synthetic samples of the camphanamide were prepared in which each of the C-1 methylene protons was replaced by deuterium. When (2S)-methionine and the C-2 deuteriated isotopomer were incubated with the enzyme in deuterium oxide and protium oxide, respectively, and the products were converted to their camphanamide derivatives and analyzed by 1H NMR spectroscopy, it was evident that decarboxylation occurred with retention of configuration at C-2. When the decarboxylation of six other substrates was studied, examination of the N-camphanamide derivatives of the amines indicated that decarboxylation occurred stereospecifically and, by analogy, with retention of configuration at C-2. When tritiated pyridoxal phosphate was incubated with the enzyme, tritiated pyridoxamine phosphate was formed. Analysis of the chirality of the methylene group at C-4' indicated that, during abortive transamination, protonation occurred from the 4'-si face of the coenzyme, the same stereochemical result as that obtained for several bona fide transaminase enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

来自绵马鳞毛蕨的L-蛋氨酸脱羧酶已从丙酮粉提取物中纯化了256倍,达到了近乎纯的状态。该酶与膜相关,在初始提取过程中需要去污剂来溶解。该酶是亚基Mr 57,000的同型二聚体,以20 mM(2S)-蛋氨酸为底物时,在约5.0的pH值下表现出最佳活性。在pH 4.5及以下时,蛋氨酸的比活性kcat约为50 mol s(-1)(每摩尔活性位点)。多种直链和支链(2S)-烷基氨基酸都是该酶的底物。然而,脱羧速率Vmax和表观米氏常数Km的值随结构和C-3处的手性而变化。已研究了三种底物(2S)-蛋氨酸、缬氨酸和亮氨酸的V和V/K对pH的依赖性。磷酸吡哆醛(PLP)是酶活性所必需的,在没有过量PLP的情况下,孵育过程中酶的活性会随时间降低。添加PLP可完全恢复活性,表明正常脱羧反应伴随着无效的脱羧-转氨反应。通过显示[35S]蛋氨酸转化为标记的3-(甲硫基)丙醛,同时[4'-3H]PLP转化为标记的磷酸吡哆胺5'-磷酸(PMP),证实了无效反应的发生。(2S)-蛋氨酸的脱羧产生了3-(甲硫基)-1-氨基丙烷。制备该胺的N-樟脑酰胺衍生物可通过1H NMR光谱区分C-1亚甲基质子。制备了樟脑酰胺的合成样品,其中每个C-1亚甲基质子都被氘取代。当分别在氧化氘和氧化氕中用(2S)-蛋氨酸和C-2氘代异构体与该酶孵育,产物转化为它们的樟脑酰胺衍生物并通过1H NMR光谱分析时,很明显脱羧反应发生时C-2处的构型保持不变。当研究其他六种底物的脱羧反应时,对胺的N-樟脑酰胺衍生物的检查表明脱羧反应具有立体特异性,并且类似地,C-2处的构型保持不变。当用氚标记的磷酸吡哆醛与该酶孵育时,形成了氚标记的磷酸吡哆胺。对C-4'处亚甲基的手性分析表明,在无效转氨过程中,质子从辅酶的4'-si面进攻,这与几种真正的转氨酶酶获得的立体化学结果相同。(摘要截短至400字)

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