Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily.

Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily.
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DOI:
10.1038/nchembio.121
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发表时间:
2008-12
影响因子:
14.8
通讯作者:
Ealick, Steven E.
Ealick, Steven E.
中科院分区:
生物学1区
文献类型:
--
作者:
Chatterjee, Abhishek;Li, Yue;Zhang, Yang;Grove, Tyler L.;Lee, Michael;Krebs, Carsten;Booker, Squire J.;Begley, Tadhg P.;Ealick, Steven E.

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4-氨基-5-羟甲基-2-甲基嘧啶磷酸合成酶(HMP-P)催化5-氨基咪唑核糖核苷酸(AIR)的复杂重排,形成磷酸硫胺的嘧啶部分HMP-P。测定了HMP-P合酶及其与产物HMP-P和底物类似物咪唑核糖肽配合物的三维结构。HMP-P合酶的结构揭示了一个同源二聚体,其中每个原聚体包括三个结构域:一个具有新褶皱的n端结构域,一个中心(βα)8桶结构域和一个包含保守的CX2CX4C基序的无序c端结构域,提示[4Fe-4S]簇。生化研究证实,HMP-P合成酶具有铁硫簇依赖性,是自由基SAM超家族的新成员,HMP-P和5 ' -脱氧腺苷是该反应的产物。Mössbauer和EPR光谱证实了一个[4Fe-4S]星团的存在。结构比较表明,HMP-P合成酶与一组腺苷钴胺自由基酶同源。这种相似性支持了这两个超级家族之间的进化关系。
4-Amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase catalyzes a complex rearrangement of 5-aminoimidazole ribonucleotide (AIR) to form HMP-P, the pyrimidine moiety of thiamin phosphate. The three-dimensional structures of HMP-P synthase and its complexes with the product HMP-P and a substrate analog imidazole ribotide were determined. The structure of HMP-P synthase reveals a homodimer in which each protomer comprises three domains: an N-terminal domain with a novel fold, a central (βα)8 barrel and a disordered C-terminal domain that contains a conserved CX2CX4C motif, suggestive of a [4Fe-4S] cluster. Biochemical studies have confirmed that HMP-P synthase is iron sulfur cluster dependent, that it is a novel member of the radical SAM superfamily and that HMP-P and 5′-deoxyadenosine are products of the reaction. Mössbauer and EPR spectroscopy confirm the presence of one [4Fe-4S] cluster. Structural comparisons reveal that HMP-P synthase is homologous to a group of adenosylcobalamin radical enzymes. This similarity supports an evolutionary relationship between these two superfamilies.
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影响因子: 5.8
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