BACTERIAL-RESISTANCE TO BETA-LACTAM ANTIBIOTICS - CRYSTAL-STRUCTURE OF BETA-LACTAMASE FROM STAPHYLOCOCCUS-AURENS PC1 AT 2.5-A RESOLUTION
BACTERIAL-RESISTANCE TO BETA-LACTAM ANTIBIOTICS - CRYSTAL-STRUCTURE OF BETA-LACTAMASE FROM STAPHYLOCOCCUS-AURENS PC1 AT 2.5-A RESOLUTION
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DOI：
10.1126/science.3107125
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发表时间：
1987-05-08
期刊：
影响因子：
56.9
通讯作者：
MOULT, J
中科院分区：
文献类型：
--
作者：
HERZBERG, O;MOULT, J
β-内酰胺酶是一种保护细菌免受β-内酰胺类抗生素致死作用的酶，因此具有相当重要的临床意义。以2.5埃分辨率测定了革兰氏阳性菌金黄色葡萄球菌PC1的β-内酰胺酶的晶体结构。它揭示了一种新的拓扑结构，由两个紧密相关的结构域组成。活性部位位于结构域之间的界面，关键的催化残基Ser70位于埋藏的螺旋的氨基末端。对活性部位凹陷内重要功能残基的处理的研究导致了底物结合的模型和丝氨酸蛋白酶的功能类比。这种不寻常的二级结构单元的拓扑结构与细菌细胞壁的β-内酰胺靶标酶的进化关系有关。
β-lactamases are enzymes that protect bacteria from the lethal effects of β-lactam antibiotics, and are therefore of considerable clinical importance. The crystal structure of β-lactamase from the Gram-positive bacteriumStaphylococcus aureusPC1 has been determined at 2.5 angstrom resolution. It reveals a molecule of novel topology, made up of two closely associated domains. The active site is located at the interface between the domains, with the key catalytic residue Ser70at the amino terminus of a buried helix. Examination of the disposition of the functionally important residues within the active site depression leads to a model for the binding of a substrate and a functional analogy to the serine proteases. The unusual topology of the secondary structure units is relevant to questions concerning the evolutionary relation to the β-lactam target enzymes of the bacterial cell wall.