Structural and Functional Analysis of Fucose-Processing Enzymes from Streptococcus pneumoniae
Structural and Functional Analysis of Fucose-Processing Enzymes from Streptococcus pneumoniae
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DOI：
10.1016/j.jmb.2013.12.006
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发表时间：
2014-04-03
影响因子：
5.6
通讯作者：
Boraston, Alisdair B.
中科院分区：
文献类型：
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作者：
Higgins, Melanie A.;Suits, Michael D.;Boraston, Alisdair B.
岩藻糖代谢途径存在于许多细菌物种中，并且通常含有中心岩藻糖加工酶岩藻糖异构酶（Fcsl）、岩藻糖激酶（FcsK）和岩藻糖-1-磷酸醛缩酶（FcsA）。岩藻糖最初通过Fcsl进行异构化，产生岩藻糖，然后通过FcsK磷酸化。FcsA将岩藻糖-1-磷酸产物切割成乳醛和磷酸二羟丙酮，其可以并入中心代谢，允许细菌使用岩藻糖作为能量来源。肺炎链球菌具有含有Fcsl、FcsK和FcsA的同源物的岩藻糖加工操纵子;然而，这种细菌似乎不能利用岩藻糖作为能量来源。为了研究这一矛盾，我们对S.肺炎球菌岩藻糖加工酶SpFcsl、SpFcsK和SpFcsA。这些酶被证明以顺序的方式起作用，最终产生二羟丙酮磷酸，并具有与其观察到的生物化学活性完全一致的结构特征。与大肠杆菌岩藻糖利用操纵子的调节类似，岩藻糖-1-磷酸似乎作为激活S.肺炎岩藻糖操纵子。尽管我们有证据表明S.肺炎链球菌似乎具有岩藻糖代谢的适当调节和生化机制，我们证实了S. pneumoniae TIGR 4菌株在岩藻糖或H-二糖上生长，这是该途径的转运蛋白的可能底物。在此基础上，我们假设S. pneumoniae岩藻糖加工途径在该细菌与其人类宿主的相互作用中具有非代谢作用。(C)2013爱思唯尔有限公司保留所有权利。
Fucose metabolism pathways are present in many bacterial species and typically contain the central fucose-processing enzymes fucose isomerase (Fcsl), fuculose kinase (FcsK), and fuculose-1-phosphate aldolase (FcsA). Fucose initially undergoes isomerization by Fcsl producing fuculose, which is then phosphorylated by FcsK. FcsA cleaves the fuculose-1-phosphate product into lactaldehyde and dihydroxyacetone phosphate, which can be incorporated into central metabolism allowing the bacterium to use fucose as an energy source. Streptococcus pneumoniae has fucose-processing operons containing homologs of Fcsl, FcsK, and FcsA; however, this bacterium appears unable to utilize fucose as an energy source. To investigate this contradiction, we performed biochemical and structural studies of the S. pneumoniae fucose-processing enzymes SpFcsl, SpFcsK, and SpFcsA. These enzymes are demonstrated to act in a sequential manner to ultimately produce dihydroxyacetone phosphate and have structural features entirely consistent with their observed biochemical activities. Analogous to the regulation of the Escherichia coli fucose utilization operon, fuculose-1-phosphate appears to act as an inducing molecule for activation of the S. pneumoniae fucose operon. Despite our evidence that S. pneumoniae appears to have the appropriate regulatory and biochemical machinery for fucose metabolism, we confirmed the inability of the S. pneumoniae TIGR4 strain to grow on fucose or on the H-disaccharide, which is the probable substrate of the transporter for the pathway. On the basis of these observations, we postulate that the S. pneumoniae fucose-processing pathway has a non-metabolic role in the interaction of this bacterium with its human host. (C) 2013 Elsevier Ltd. All rights reserved.