Allosteric regulation of substrate channeling: Salmonella typhimurium tryptophan synthase.
Allosteric regulation of substrate channeling: Salmonella typhimurium tryptophan synthase.
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DOI：
10.3389/fmolb.2022.923042
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发表时间：
2022
影响因子：
5
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中科院分区：
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肠道细菌对L-色氨酸(L-色氨酸)合成的调控始于基因表达水平，L-色氨酸的细胞浓度密切控制着负责合成L-色氨酸的色氨酸操纵子的五种酶的表达。其中两种酶，Trpa和TrpB，形成αββα双酶复合体，命名为色氨酸合成酶(TS)。TS执行最后两个酶过程，包括合成L-色氨酸。TSα亚基催化3-吲哚D-甘油醛3‘-磷酸裂解成吲哚和D-甘油醛3-磷酸；需要β的吡哆醛亚基催化九步反应序列，以吲哚取代L-丝氨酸羟基，得到L-色氨酸和一个水分子。在αβ双酶复合体的αββα二聚体单元内，共同的中间体吲哚通过一条相互连接的25埃长的隧道从α位点输送到β位点。TS系统提供了变构控制的不同寻常的例子，其中沿β反应催化路径的九种不同共价中间体的结构和与α位点结合的底物提供了用于将αββα系统在开放(T)和闭合(R)变构状态之间切换的变构触发器。这种触发提供了一种连接，将变构构象坐标耦合到α-和β-位置的共价化学反应坐标。这种偶联驱动T和R构象之间的α和β-位，以实现底物结合和/或产物释放的调节，调节α和β位的催化活性，防止吲哚从活性位和相互连接的隧道的限制中逃逸，以及α和β位催化活性的同步。本文综述了近年来在鼠伤寒沙门氏菌中发现的复合体的结构、功能和变构调节之间的关系的研究进展。
The regulation of the synthesis of L-tryptophan (L-Trp) in enteric bacteria begins at the level of gene expression where the cellular concentration of L-Trp tightly controls expression of the five enzymes of the Trp operon responsible for the synthesis of L-Trp. Two of these enzymes, trpA and trpB, form an αββα bienzyme complex, designated as tryptophan synthase (TS). TS carries out the last two enzymatic processes comprising the synthesis of L-Trp. The TS α-subunits catalyze the cleavage of 3-indole D-glyceraldehyde 3′-phosphate to indole and D-glyceraldehyde 3-phosphate; the pyridoxal phosphate-requiring β-subunits catalyze a nine-step reaction sequence to replace the L-Ser hydroxyl by indole giving L-Trp and a water molecule. Within αβ dimeric units of the αββα bienzyme complex, the common intermediate indole is channeled from the α site to the β site via an interconnecting 25 Å-long tunnel. The TS system provides an unusual example of allosteric control wherein the structures of the nine different covalent intermediates along the β-reaction catalytic path and substrate binding to the α-site provide the allosteric triggers for switching the αββα system between the open (T) and closed (R) allosteric states. This triggering provides a linkage that couples the allosteric conformational coordinate to the covalent chemical reaction coordinates at the α- and β-sites. This coupling drives the α- and β-sites between T and R conformations to achieve regulation of substrate binding and/or product release, modulation of the α- and β-site catalytic activities, prevention of indole escape from the confines of the active sites and the interconnecting tunnel, and synchronization of the α- and β-site catalytic activities. Here we review recent advances in the understanding of the relationships between structure, function, and allosteric regulation of the complex found in Salmonella typhimurium.