Mechanistic insights into water activation in SAM hydroxide adenosyltransferase (duf-62).
Mechanistic insights into water activation in SAM hydroxide adenosyltransferase (duf-62).
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SAM氢氧化物腺基转移酶（DUF-62）中水活化的机械洞察力。
DOI：
10.1002/cbic.200900369
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发表时间：
2009-10-12
期刊：
影响因子：
3.2
通讯作者：
O'Hagan, David
中科院分区：
文献类型：
--
作者：
Deng, Hai;McMahon, Stephen A.;Eustaquio, Alessandra S.;Moore, Bradley S.;Naismith, James H.;O'Hagan, David
在碳上介导SN 2取代反应的酶相对罕见。[1]然而，S-腺苷-L-甲硫氨酸（SAM）由于其锍部分和所得硫醚的离去基团倾向而易于取代。[2]已经鉴定了不同的酶，其催化SAM的所有三个碳（C5′、Me、Cγ）处的亲核攻击，所述三个碳位于与该锍硫相邻的位置（方案1）。甲基转移酶类利用C、N、O、S亲核试剂攻击锍Me以使SAM脱甲基并产生S-腺苷-L-高半胱氨酸（SAH）。[3]亚精胺[4]和精胺[5]脱氢酶催化氨丙基亲核试剂攻击脱羧S-腺苷-L-甲硫氨酸（dcadenosyl-L-methionine，dcadenosM）的Cγ甲硫氨酰臂，这是多胺生物合成过程中的一个重要反应。[6]两种酶，来自Streptomyces cattleya [7，8]的氟酶和来自Salinispora tropica [9]的氯酶，催化SAM的C5′处的卤离子SN 2取代，分别生成5′-氟-5 ′-脱氧腺苷和5′-氯-5 ′-脱氧腺苷（示意图1）。氟酶和氯酶都参与各自生物体中卤素代谢物生物合成的第一步。这些酶有30%的同源性，属于一个大的微生物超家族，被注释为未知功能域-62（duf-62）。我们最近证明了这个超家族的非卤化成员异常地催化SAM的C5′碳上的水（氢氧化物）的亲核攻击，以生成腺苷和L-甲硫氨酸。[10与腺苷复合的四种非卤化duf-62蛋白质的结构已经被保藏。[2，10]正如预期的那样，它们具有与氟化酶和氯化酶结构相同的折叠;这证实了它们的进化关系。然而，duf-62具有高度保守的活性位点，包括His-Arg-Asp三联体氨基酸，这在超家族的两个卤化（氟化酶和氯化酶）成员中没有发现，这是它们之间的显著差异。
Enzymes that mediate SN2 substitution reactions at carbon are relatively rare.[1] S-Adenosyl-L-methionine (SAM) is, however, amenable to substitution, due to its sulfonium moiety and the leaving group propensity of the resultant thioether.[2] Different enzymes have been identified that catalyse nucleophilic attack at all three carbons (C5′, Me, Cγ) of SAM positioned adjacent to this sulfonium sulfur (Scheme 1). The methyltransferase enzyme class attacks the sulfonium Me utilising C, N, O, S nucleophiles to demethylate SAM and generate S-adenosyl-L-homocysteine (SAH).[3] Spermidine [4] and spermine [5] synthases catalyse the attack of aminopropyl nucleophiles at the Cγ methionyl arm of decarboxylated S-adenosyl-L-methionine (dcAdoM)—an important reaction during polyamine biosynthesis.[6] Two enzymes, the fluorinase from Streptomyces cattleya [7, 8] and the chlorinase from Salinispora tropica [9] catalyse halide ion SN2 substitution at the C5′ of SAM to generate 5′-fluoro-5′-deoxyadenosine and 5′-chloro-5′-deoxyadenosine, respectively (Scheme 1).Both the fluorinase and chlorinase enzymes are involved in the first step of halogen metabolite biosynthesis in their respective organisms. These enzymes share 30% homology and belong to a large microbial superfamily, which is annotated as domains of unknown function-62 (duf-62). We have recently demonstrated that the nonhalogenating members of this superfamily unusually catalyse nucleophilic attack of water (hydroxide) at the C5′ carbon of SAM to generate adenosine and L-methionine.[10, 11] Structures of four nonhalogenating duf-62 proteins in complex with adenosine have been deposited.[2, 10] As expected they have the same fold as the fluorinase and chlorinase structures; this confirms their evolutionary relationship. However, the duf-62s have highly conserved active sites including a His–Arg–Asp triad of amino acids that are not found in the two halogenating (fluorinase and chlorinase) members of the superfamily, a striking difference between these
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.9
作者：
Wu, Hong;Min, Jinrong;Plotnikov, Alexander N.
通讯作者：
Plotnikov, Alexander N.
影响因子：
3.2
作者：
Eustaquio, Alessandra S.;Haerle, Johannes;Noel, Joseph P.;Moore, Bradley S.
通讯作者：
Moore, Bradley S.
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
14.8
作者：
Eustaquio, Alessandra S.;Pojer, Florence;Moore, Bradley S.
通讯作者：
Moore, Bradley S.