Smith Clyde A
Stanford Synchrotron Radiation Laboratory, Menlo Park, CA 94025, USA.
J Mol Biol. 2006 Sep 29;362(4):640-55. doi: 10.1016/j.jmb.2006.07.066. Epub 2006 Aug 1.
For bacteria, the structural integrity of its cell wall is of utmost importance for survival, and to this end, a rigid scaffold called peptidoglycan, comprised of sugar molecules and peptides, is synthesized and located outside the cytoplasmic membrane of the cell. Disruption of this peptidoglycan layer has for many years been a prime target for effective antibiotics, namely the penicillins and cephalosporins. Because this rigid layer is synthesized by a multi-step pathway numerous additional targets also exist that have no counterpart in the animal cell. Central to this pathway are four similar ligase enzymes, which add peptide groups to the sugar molecules, and interrupting these steps would ultimately prove fatal to the bacterial cell. The mechanisms of these ligases are well understood and the structures of all four of these ligases are now known. A detailed comparison of these four enzymes shows that considerable conformational changes are possible and that these changes, along with the recruitment of two different N-terminal binding domains, allows these enzymes to bind a substrate which at one end is identical and at the other has the growing polypeptide tail. Some insights into the structure-function relationships in these enzymes is presented.
对于细菌而言，其细胞壁的结构完整性对生存至关重要。为此，一种由糖分子和肽组成的名为肽聚糖的刚性支架在细胞的细胞质膜外合成并定位。多年来，破坏这种肽聚糖层一直是有效抗生素（即青霉素和头孢菌素）的主要作用靶点。由于这种刚性层是通过多步途径合成的，因此还存在许多在动物细胞中没有对应物的其他靶点。该途径的核心是四种相似的连接酶，它们将肽基团添加到糖分子上，中断这些步骤最终将证明对细菌细胞是致命的。这些连接酶的机制已得到充分了解，并且现在已知所有这四种连接酶的结构。对这四种酶的详细比较表明，它们可能发生相当大的构象变化，并且这些变化与两种不同的N端结合结构域的募集一起，使这些酶能够结合一种底物，该底物一端相同而另一端具有不断增长的多肽尾巴。本文介绍了对这些酶中结构 - 功能关系的一些见解。
