Yan Y, Munshi S, Leiting B, Anderson M S, Chrzas J, Chen Z
Department of Structural Biology, West Point, PA, 19486, USA.
J Mol Biol. 2000 Dec 1;304(3):435-45. doi: 10.1006/jmbi.2000.4215.
MurF is required to catalyze the final step in the synthesis of the cytoplasmic precursor of the bacterial cell wall peptidoglycan, rendering it an attractive target for antibacterial drug development. The crystal structure of the MurF apo-enzyme has been determined using the multiwavelength anomalous dispersion method and refined to 2.3 A resolution. It contains three consecutive open alpha/beta-sheet domains. In comparison with the complex crystal structures of MurD and its substrates, The topology of the N-terminal domain of MurF is unique, while its central and C-terminal domains exhibit similar mononucleotide and dinucleotide-binding folds, respectively. The apo-enzyme of MurF crystal structure reveals an open conformation with the three domains juxtaposed in a crescent-like arrangement creating a wide-open space where substrates are expected to bind. As such, catalysis is not feasible and significant domain closure is expected upon substrate binding.
MurF是催化细菌细胞壁肽聚糖细胞质前体合成最后一步所必需的，这使其成为抗菌药物开发的一个有吸引力的靶点。MurF脱辅基酶的晶体结构已通过多波长反常色散法确定，并精修至2.3埃分辨率。它包含三个连续的开放α/β折叠结构域。与MurD及其底物的复合晶体结构相比，MurF N端结构域的拓扑结构独特，而其中央和C端结构域分别呈现出类似的单核苷酸和二核苷酸结合折叠。MurF晶体结构的脱辅基酶显示出一种开放构象，三个结构域以新月状排列并列，形成一个宽敞的开放空间，底物有望在此结合。因此，催化作用不可行，预计底物结合后结构域会发生显著闭合。
