How Sugars Pucker: Electronic Structure Calculations Map the Kinetic Landscape of Five Biologically Paramount Monosaccharides and Their Implications for Enzymatic Catalysis
How Sugars Pucker: Electronic Structure Calculations Map the Kinetic Landscape of Five Biologically Paramount Monosaccharides and Their Implications for Enzymatic Catalysis
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DOI：
10.1021/ja410264d
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发表时间：
2014-01-22
影响因子：
15
通讯作者：
Beckham, Gregg T.
中科院分区：
文献类型：
--
作者：
Mayes, Heather B.;Broadbelt, Linda J.;Beckham, Gregg T.
糖苷水解酶（GH）在糖苷键的裂解过程中沿着沿着特定的“催化路线”扭曲碳水化合物环的几何形状，说明。底物构象与反应活性的关系。以前的理论研究热力学孤立单糖提供洞察特定糖的催化行程。然而，碳水化合物起皱构象的动力学可及性和环外基团的作用尚未得到彻底解决。在这里，我们提出了第一个完整的图书馆的低能量本地最小值和puckering相互转换过渡态的五个生物相关的吡喃糖：β-木糖，β-甘露糖，α-葡萄糖，β-葡萄糖，和β-N-乙酰葡糖胺。这些都是通过深入的理论研究得到的38 IUPAC指定的puckering几何和所有可能的构象的环外基团。这些计算表明，环外基团时，必须明确考虑这些相互转换途径。此外，这些数据使以前的假设，为什么酶扰动环的几何形状从低能赤道椅（C-4（1））构象的评价。他们表明，相对热力学单独不普遍与GH催化行程。对于一些糖，特定的起皱物提供催化有利的电子结构性质，例如异头碳部分电荷，和低动力学势垒以实现给定的起皱构象。然而，不同的因素与其他糖的催化行程相关;对于β-N-乙酰葡糖胺，关键的N-乙酰基臂混淆了褶皱景观，似乎是关键因素。总的来说，这项研究揭示了一个更全面的理解，为什么特定的褶皱几何形状是有利的碳水化合物催化伴随着糖生物学的复杂性。
Glycoside hydrolases (GHs) distort carbohydrate ring geometry along particular "catalytic itineraries" during the cleavage of glycosidic bonds, illustrating. the relationship between substrate conformation and reactivity. Previous theoretical studies of thermodynamics of isolated monosaccharides offer insights into the catalytic itineraries of particular sugars. However, kinetic accessibility of carbohydrate puckering conformations and the role of exocyclic groups have not yet been thoroughly addressed. Here we present the first complete library of low-energy local minima and puckering interconversion transition states for five biologically relevant pyranose sugars: beta-xylose, beta-mannose, alpha-glucose, beta-glucose, and beta-N-acetylglucosamine. These were obtained by a thorough theoretical investigation each of the 38 IUPAC designated puckering geometries and all possible conformations of the exocyclic groups. These calculations demonstrate that exocyclic groups must be explicitly considered when examining these interconversion pathways. Furthermore, these data enable evaluation of previous hypotheses of why enzymes perturb ring geometries from the low-energy equatorial chair (C-4(1)) conformation. They show that the relative thermodynamics alone do not universally correlate with GH catalytic itineraries. For some sugars, particular puckers offer both catalytically favorable electronic structure properties, such as anomeric carbon partial charge, and low kinetic barriers to achieve a given puckering conformation. However, different factors correlate with catalytic itineraries for other sugars; for beta-N-acetylglucosamine, the key N-acetyl arm confounds the puckering landscape and appears to be the crucial factor. Overall, this study reveals a more comprehensive understanding of why particular puckering geometries are favored in carbohydrate catalysis concomitant with the complexity of glycobiology.