The flavoprotein MrsD catalyzes the oxidative decarboxylation reaction involved in formation of the peptidoglycan biosynthesis inhibitor mersacidin
The flavoprotein MrsD catalyzes the oxidative decarboxylation reaction involved in formation of the peptidoglycan biosynthesis inhibitor mersacidin
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DOI：
10.1128/jb.184.5.1234-1243.2002
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发表时间：
2002-03-01
影响因子：
3.2
通讯作者：
Kupke, T
中科院分区：
文献类型：
--
作者：
Majer, F;Schmid, DG;Kupke, T
1抗生素Merceidin通过与肽聚糖前体脂质II结合来抑制肽聚糖的生物合成。Meracidin含有一个不饱和的硫醚桥，它被认为是通过翻译后修饰+15苏氨酸残基和Merceidin前体多肽MRSA的COOH-末端半胱氨酸残基来合成的。我们发现，黄素蛋白mrsD催化MRSA的COOH末端半胱氨酸残基氧化脱羧基为氨基硫醇残基。MRS D属于最近报道的含黄素的同源低聚半胱氨酸脱羧酶家族(即HFCD蛋白家族)。这个蛋白质家族的成员包括细菌DFP蛋白(参与辅酶A的生物合成)，真核耐盐蛋白，以及进一步的氧化脱羧酶，如EpiD。与EpiD和DFP不同的是，mrsD是一种时尚，而不是依赖于FMN的黄素蛋白。HFCD酶的特征是具有保守的His残基，它是活性部位的一部分。用这一His残基交换ASN导致了MRS D的失活。抗生素合成酶EpiD和mrsD具有不同的底物特异性。
The lantibiotic mersacidin inhibits peptidoglycan biosynthesis by binding to the peptidoglycan precursor lipid II. Mersacidin contains an unsaturated thioether bridge, which is proposed to be synthesized by post-translational modifications of threonine residue +15 and the COOH-terminal cysteine residue of the mersacidin precursor peptide MrsA. We show that the flavoprotein MrsD catalyzes the oxidative decarboxylation of the COOH-terminal cysteine residue of MrsA to an aminoenethiol residue. MrsD belongs to the recently described family of homo-oligomeric flavin-containing Cys decarboxylases (i.e., the HFCD protein family). Members of this protein family include the bacterial Dfp proteins (which are involved in coenzyme A biosynthesis), eukaryotic salt tolerance proteins, and further oxidative decarboxylases such as EpiD. In contrast to EpiD and Dfp, MrsD is a FAD and not an FMN-dependent flavoprotein. HFCD enzymes are characterized by a conserved His residue which is part of the active site. Exchange of this His residue for Asn led to inactivation of MrsD. The lantibiotic-synthesizing enzymes EpiD and MrsD have different substrate specificities.