肉碱octanoyltransferase malonyl-CoA-binding站点的结构模型和肉碱palmitoyltransferase我:突变分析malonyl-CoA关联域。
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Morillas M, Gomez-Puertas P, B Rubi Clotet J, Arino J,瓦伦西亚,Hegardt FG, Serra D,正如G
肉碱octanoyltransferase malonyl-CoA-binding站点的结构模型和肉碱palmitoyltransferase我:突变分析malonyl-CoA关联域。
277年J生物化学杂志。2002年3月29日,(13):11473 - 80。Epub 2002 1月14。
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11790793 (在PubMed]
- 文摘
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肉碱octanoyltransferase (COT)和肉碱palmitoyltransferase (CPT)我,方便运输的中期和长链脂肪酸通过过氧化物酶病和线粒体膜,由malonyl-CoA生理抑制。使用一个“硅”大分子对接方法,我们建立了一个模型malonyl-CoA可以附加在催化核心附近。这扰乱了酰基辅酶衬底的定位模型中的频道报道对蛋白质(Morillas, M。Gomez-Puertas, P。罗卡角,R。塞拉,D。最佳翻译,G。瓦伦西亚,。,Hegardt f . g .(2001)生物。276年化学,45001 - 45008)。假定的malonyl-CoA域包含他的(340),一起涉及他在床(131)malonyl-CoA敏感性(Morillas, M。Clotet, J。Rubi, B。塞拉,D。最佳翻译,G。Arino, J。和Hegardt f . g .(2000) 2月。466年,183 - 186)。 When we mutated COT His(131) the IC(50) increased, and malonyl-CoA competed with the substrate decanoyl-CoA. Mutation of COT Ala(332), present in the domain 8 amino acids away from His(340), decreased the malonyl-CoA sensitivity of COT. The homologous histidine and alanine residues of L-CPT I, His(277), His(483), and Ala(478) were also mutated, which decreased malonyl-CoA sensitivity. Natural mutation of Pro(479), which is also located in the malonyl-CoA predicted site, to Leu in a patient with human L-CPT I hereditary deficiency, modified malonyl-CoA sensitivity. We conclude that this malonyl-CoA domain is present in both COT and L-CPT I proteins and might be the site at which malonyl-CoA interacts with the substrate acyl-CoA. Other malonyl-CoA non-inhibitable members of the family, CPT II and carnitine acetyltransferase, do not contain this domain.