The activating oxydianion binding domain for enzyme-catalyzed proton transfer, hydride transfer, and decarboxylation: specificity and enzyme architecture.
The activating oxydianion binding domain for enzyme-catalyzed proton transfer, hydride transfer, and decarboxylation: specificity and enzyme architecture.
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用于酶催化的质子转移，氢化物转移和脱羧的活化氧结合结构域：特异性和酶结构。
DOI：
10.1021/ja5123842
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发表时间：
2015-01-28
影响因子：
15
通讯作者：
Richard, John P.
中科院分区：
文献类型：
--
作者：
Reyes, Archie C.;Zhai, Xiang;Morgan, Kelsey T.;Reinhardt, Christopher J.;Amyes, Tina L.;Richard, John P.
本文报道了磷酸丙糖异构酶（ScTIM）、乳清酸核苷单磷酸脱羧酶（ScOMPDC）和人肝甘油3-磷酸脱氢酶（hIGPDH）催化磷酸二氢阴离子截短底物的动力学参数。含氧阴离子与这些未配体的酶结合较弱，与过渡态复合物（E·S）结合紧密，其固有的含氧阴离子吉布斯结合自由能范围为−8.4 kcal/mol（用于激活hIGPDH催化的FPO 32-还原乙醇醛）至−3.0 kcal/mol（用于激活ScOMPDC催化的HOPO 32-脱羧1-β-d-赤呋喃糖基）乳清酸）。观察到不同氧阴离子结合结构域的特异性存在微小差异。我们提出，与ScTIM和ScOMPDC的活化相比，FPO 32-和S2 O32-分别活化hIGPDH的大的−8.4 kcal/mol和小的−3.8 kcal/mol固有二价氧阴离子结合能反映了二价氧阴离子−F和−S与hIGPDH的R269阳离子侧链之间的稳定和不稳定相互作用。这些结果与ScTIM、ScOMPDC和hlGPDH的类似结构的氧阴离子结合结构域的隐藏功能一致。每种酶都利用与四面体无机氧阴离子的相互作用来驱动构象变化，该构象变化将底物锁定在笼状米氏复合物中，该笼状米氏复合物提供不同酶过渡态的最佳稳定。通过稳定活性笼状米氏复合物来观察二价阴离子活化可以推广到许多其他酶，这些酶利用底物结合能来驱动酶构象的变化，从而诱导紧密的底物拟合。
The kinetic parameters for activation of yeast triosephosphate isomerase (ScTIM), yeast orotidine monophosphate decarboxylase (ScOMPDC), and human liver glycerol 3-phosphate dehydrogenase (hlGPDH) for catalysis of reactions of their respective phosphodianion truncated substrates are reported for the following oxydianions: HPO32–, FPO32–, S2O32–, SO42– and HOPO32–. Oxydianions bind weakly to these unliganded enzymes and tightly to the transition state complex (E·S‡), with intrinsic oxydianion Gibbs binding free energies that range from −8.4 kcal/mol for activation of hlGPDH-catalyzed reduction of glycolaldehyde by FPO32– to −3.0 kcal/mol for activation of ScOMPDC-catalyzed decarboxylation of 1-β-d-erythrofuranosyl)orotic acid by HOPO32–. Small differences in the specificity of the different oxydianion binding domains are observed. We propose that the large −8.4 kcal/mol and small −3.8 kcal/mol intrinsic oxydianion binding energy for activation of hlGPDH by FPO32– and S2O32–, respectively, compared with activation of ScTIM and ScOMPDC reflect stabilizing and destabilizing interactions between the oxydianion −F and −S with the cationic side chain of R269 for hlGPDH. These results are consistent with a cryptic function for the similarly structured oxydianion binding domains of ScTIM, ScOMPDC and hlGPDH. Each enzyme utilizes the interactions with tetrahedral inorganic oxydianions to drive a conformational change that locks the substrate in a caged Michaelis complex that provides optimal stabilization of the different enzymatic transition states. The observation of dianion activation by stabilization of active caged Michaelis complexes may be generalized to the many other enzymes that utilize substrate binding energy to drive changes in enzyme conformation, which induce tight substrate fits.
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影响因子：
2.9
作者：
Alahuhta, Markus;Wierenga, Rik K.
通讯作者：
Wierenga, Rik K.
影响因子：
5.6
作者：
Axe, Jennifer M.;Boehr, David D.
通讯作者：
Boehr, David D.
酶体系结构：酶激活5'-单磷酸酯脱羧酶的酶激活磷酸二苯二醇相互作用的解构。
影响因子：
15
作者：
Goldman, Lawrence M.;Amyes, Tina L.;Goryanova, Bogdana;Gerlt, John A.;Richard, John P.
通讯作者：
Richard, John P.
DOI：
10.1073/pnas.1111252108
发表时间：
2011-08-23
影响因子：
11.1
作者：
Adamczyk, Andrew J.;Cao, Jie;Warshel, Arieh
通讯作者：
Warshel, Arieh
影响因子：
4.8
作者：
Chaganti, Lalith K.;Kuppili, Raja Reddy;Bose, Kakoli
通讯作者：
Bose, Kakoli