Roy R S, Kim S, Baleja J D, Walsh C T
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Chem Biol. 1998 Apr;5(4):217-28. doi: 10.1016/s1074-5521(98)90635-4.
The peptide antibiotic microcin B17 (MccB17) contains oxazole and thiazole heterocycles formed by the post-translational modification of four cysteine and four serine residues. An amino-terminal propeptide targets the 69 amino acid precursor of MccB17 (preproMccB17) to the heterocyclization enzyme MccB17 synthetase. The mode of synthetase recognition has been unclear, because there has been limited structural information available on the MccB17 propeptide to date.
The solution structure of the MccB17 propeptide (McbA1-26), determined using nuclear magnetic resonance, reveals that McbA1-26 is an amphipathic alpha helix. Mutational analysis of 13 propeptide residues showed that Phe8 and Leu12 are essential residues for MccB17 synthetase recognition. A domain of the propeptide was putatively identified as the region that interacts with the synthetase.
MccB17 synthetase recognizes key hydrophobic residues within a helical propeptide, allowing the selective heterocyclization of downstream cysteine and serine residues in preproMccB17. The determination of the solution structure of the propeptide should facilitate the investigation of other functions of the propeptide, including a potential role in antibiotic secretion.
肽抗生素小菌素B17（MccB17）含有由四个半胱氨酸和四个丝氨酸残基经翻译后修饰形成的恶唑和噻唑杂环。氨基末端前肽将MccB17的69个氨基酸前体（前原MccB17）靶向至杂环化酶MccB17合成酶。由于迄今为止关于MccB17前肽的结构信息有限，合成酶的识别模式尚不清楚。
使用核磁共振确定的MccB17前肽（McbA1 - 26）的溶液结构表明，McbA1 - 26是一个两亲性α螺旋。对13个前肽残基的突变分析表明，Phe8和Leu12是MccB17合成酶识别的必需残基。前肽的一个结构域被推测为与合成酶相互作用的区域。
MccB17合成酶识别螺旋前肽内的关键疏水残基，从而使前原MccB17中下游的半胱氨酸和丝氨酸残基进行选择性杂环化。前肽溶液结构的确定应有助于研究前肽的其他功能，包括其在抗生素分泌中的潜在作用。
