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首页> 外文期刊>Biochemistry >STRUCTURE OF THE 70-KDA SOLUBLE LYTIC TRANSGLYCOSYLASE COMPLEXED WITH BULGECIN A - IMPLICATIONS FOR THE ENZYMATIC MECHANISM
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STRUCTURE OF THE 70-KDA SOLUBLE LYTIC TRANSGLYCOSYLASE COMPLEXED WITH BULGECIN A - IMPLICATIONS FOR THE ENZYMATIC MECHANISM

机译：球藻毒素A复合的70-KDA可溶性溶菌转糖基转移酶的结构-对酶机制的启示。

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摘要

Bulgecins are O-sulfonated glycopeptides that are able to enhance the antibacterial activity of beta-lactam antibiotics. The 70-kDa soluble lytic transglycosylase (SLT70) from Escherichia coli forms a specific target of these compounds. Using X-ray crystallography, the three-dimensional structure of a complex of SLT70 with bulgecin A has been determined to 2.8-Angstrom resolution and refined to an R factor of 19.5%. The model contains all 618 amino acids of SLT70 and a single molecule of bound bulgecin, located in the active site of the enzyme. The glycopeptide inhibitor is bound in an extended conformation : occupying sites analogous to the B, C, and D subsites of lysozyme. Upon binding of bulgecin, the three-stranded antiparallel beta-sheet in the C domain shows a pronounced shift toward the inhibitor. In subsite D, the proposed catalytic residue Glu478 forms a hydrogen bond to the hydroxymethyl oxygen of the proline part of bulgecin and interacts electrostatically with the proline NH2+ group. These interactions, in addition to the interactions observed for the 2-acetamido group of the N-acetylglucosamine residue bound in subsite C, may explain the strong inhibition of SLT70 activity by bulgecin, suggesting that bulgecin acts as an analogue of an oxocarbonium intermediate in the reaction catalyzed by SLT70. The structure of the SLT70-bulgecin A complex may be of assistance in the rational design of novel antibiotics.
机译：球蛋白是O磺化的糖肽，能够增强β-内酰胺类抗生素的抗菌活性。来自大肠杆菌的70 kDa可溶性裂解转糖基酶（SLT70）构成了这些化合物的特定靶标。使用X射线晶体学，已确定SLT70与bulgecin A的复合物的三维结构，分辨率为2.8埃，并精炼为19.5％的R因子。该模型包含SLT70的全部618个氨基酸和位于该酶活性位点的结合的球蛋白的单个分子。糖肽抑制剂以扩展的构象结合：占据类似于溶菌酶的B，C和D亚位的位点。结合bulgecin后，C结构域中的三链反平行β-折叠显示出明显的向抑制剂的转变。在亚位点D中，拟议的催化残基Glu478与bulgecin脯氨酸部分的羟甲基氧形成氢键，并与脯氨酸NH2 +发生静电相互作用。除了在位点C结合的N-乙酰氨基葡糖残基的2-乙酰氨基基团上观察到的相互作用外，这些相互作用还可能解释了bulgecin对SLT70活性的强烈抑制作用，这表明bulgecin充当了碳氧化合物中间体碳氧化合物的类似物。 SLT70催化反应。 SLT70-bulgecin A复合物的结构可能有助于合理设计新型抗生素。

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