Structural insights into the function of the nicotinate mononucleotide:phenol/p-cresol phosphoribosyltransferase (ArsAB) enzyme from Sporomusa ovata.
Structural insights into the function of the nicotinate mononucleotide:phenol/p-cresol phosphoribosyltransferase (ArsAB) enzyme from Sporomusa ovata.
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对卵形孢子烟酸单核苷酸：苯酚/对甲酚磷酸核糖基转移酶 (ArsAB) 功能的结构见解。
DOI：
10.1021/bi301142h
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Rayment,Ivan
中科院分区：
文献类型：
--
作者：
Newmister,SeanA;Chan,ChiHo;Escalante-Semerena,JorgeC;Rayment,Ivan
钴酰胺 (Cbas) 是含钴 (Co) 的四吡咯衍生物，参与酶催化的碳骨架重排、甲基转移和还原脱卤。钴酰胺的生物合成很复杂并且仅由一些细菌和荠菜进行。 Cobamides 具有上部 (Coβ) 配体（5'-脱氧腺苷基或甲基）和下部 (Coα) 配体碱基，有助于轴向 Co 配位。低级 Coα 配体的身份根据合成 Cbas 的生物体而变化。同型产乙酸细菌Sporomusa ovata合成两种独特的酚醛酰胺（即Coα-（酚基/对甲酚基）钴酰胺），该细菌用于甲醇和3,4-二甲氧基苯甲酸酯的分解代谢。 TheS。 ovataArsAB 酶在掺入考巴酰胺之前激活酚类低级配体。 ArsAB 由两个亚基组成，这两个亚基均与已充分表征的肠沙门氏菌 CobT 酶同源（约 35% 同一性），该酶可转移含氮碱基，例如 5,6-二甲基苯并咪唑 (DMB) 和腺嘌呤，但不能利用酚类物质。在这里，我们报告了 ArsAB 的三维结构，表明该酶形成假对称异二聚体，提供了只有 ArsA 亚基具有碱基：磷酸核糖基转移酶活性的证据，并提出了一种通过活化的水分子促进酚类转移的机制。
Cobamides (Cbas) are cobalt (Co) containing tetrapyrrole-derivatives involved in enzyme-catalyzed carbon skeleton rearrangements, methyl-group transfers, and reductive dehalogenation. The biosynthesis of cobamides is complex and is only performed by some bacteria and achaea. Cobamides have an upper (Coβ) ligand (5′-deoxyadenosyl or methyl) and a lower (Coα) ligand base that contribute to the axial Co coordinations. The identity of the lowerCoαligand varies depending on the organism synthesizing the Cbas. The homoacetogenic bacteriumSporomusa ovatasynthesizes two unique phenolic cobamides (i.e., Coα-(phenolyl/p-cresolyl)cobamide), which are used in the catabolism of methanol and 3,4-dimethoxybenzoate by this bacterium. TheS. ovataArsAB enzyme activates a phenolic lower ligand prior to its incorporation into the cobamide. ArsAB consists of two subunits, both of which are homologous (∼35% identity) to the well-characterizedSalmonella entericaCobT enzyme, which transfers nitrogenous bases such as 5,6-dimethylbenzimidazole (DMB) and adenine, but cannot utilize phenolics. Here we report the three-dimensional structure of ArsAB, which shows that the enzyme forms a pseudosymmetric heterodimer, provide evidence that only the ArsA subunit has base:phosphoribosyl-transferase activity, and propose a mechanism by which phenolic transfer is facilitated by an activated water molecule.