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Mycothiol biochemistry.

机译:硫羟硫醇生物化学。

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Mycothiol (MSH) is a novel thiol comprised of N-acetylcysteine amide-linked to GlcN-alpha(1-1)-Ins. It is the major thiol in most actinomycetes and is produced at millimolar levels in mycobacteria and streptomycetes. MSH biosynthesis occurs by linkage of GlcNAc to Ins, deacetylation to GlcN-Ins, ligation of the latter to L-cysteine, and transacetylation of the cysteinyl residue by CoASAc to produce MSH. The genes encoding the respective enzymes have been designated mshA, mshB, mshC, and mshD; all but mshA have been identified. Mycobacterium smegmatis mutants deficient in mshA, mshC, and mshD have been characterized. MSH plays a significant role in the detoxification of thiol-reactive substances, including formaldehyde, various electrophiles, and antibiotics. Mycothiol S-conjugates derived from electrophiles and antibiotics are cleaved by mycothiol S-conjugate amidase to release GlcN-Ins, used to resynthesize MSH, and a mercapturic acid which is excreted from the cell. A mycothiol-disulfide-selective reductase has been identified and likely helps to maintain cellular MSH in the reduced state. Mycothiol biochemistry has characteristics similar to those of glutathione but also has a variety of unique features.
机译:麦考硫醇(MSH)是一种新型的巯基,由N-乙酰半胱氨酸酰胺连接到GlcN-alpha(1-1)-Ins组成。它是大多数放线菌中的主要硫醇,在分枝杆菌和链霉菌中以毫摩尔水平产生。 MSH生物合成是通过GlcNAc与Ins的连接,与GlcN-Ins的脱乙酰基作用,GlcN-Ins与L-半胱氨酸的连接以及CoASAc对半胱氨酰残基的反乙酰化作用产生的MSH而发生的。编码相应酶的基因已命名为mshA,mshB,mshC和mshD;除mshA以外的所有其他都已被识别。已经鉴定了缺乏mshA,mshC和mshD的耻垢分枝杆菌突变体。 MSH在包括甲醛,各种亲电试剂和抗生素在内的硫醇反应性物质的解毒中起着重要作用。衍生自亲电子试剂和抗生素的霉菌硫醇S-缀合物被霉菌硫醇S-缀合物酰胺酶裂解,释放出GlcN-Ins(用于重新合成MSH)和巯基酸,后者从细胞中排出。已经确定了一种硫羟硫醇-二硫键选择性还原酶,它可能有助于将细胞MSH维持在还原状态。麦硫酚的生物化学具有与谷胱甘肽相似的特征,但也具有多种独特的特征。

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