【大師講壇】第232期 | 新型酶催化機(jī)制的計算探索
日期：2024-10-30
閱讀：901
嘉賓簡介
K. N. Houk received his Ph.D. at Harvard, working with R. B. Woodward on experimental tests of orbital symmetry selection rules. He has taught at Louisiana State University, the University of Pittsburgh, and UCLA since 1986. From 1988-1990, he was Director of the Chemistry Division of the National Science Foundation. He was the UCLA Saul Winstein Chair in Organic Chemistry from 2009-2021, and is now Distinguished Research Professor. Beginning as an experimental organic chemist, he evolved over his career into a theoretical and computational organic chemist, involved in collaborations with groups all over the world. He is an elected member of the US National and Chinese Academies of Science. He has more than 1500 publications.
Kendall N. Houk 在哈佛大學(xué)獲得了學(xué)士、碩士和博士學(xué)位，期間與 R. B. Woodward 共同研究軌道對稱選擇規(guī)則的實驗測試。1968年，加入路易斯安那州立大學(xué)任教，1980年轉(zhuǎn)至匹茲堡大學(xué)，1986年加入加州大學(xué)洛杉磯分校（UCLA）。1988年至1990年，擔(dān)任美國國家科學(xué)基金會化學(xué)部主任。1991年至1994年，擔(dān)任 UCLA 化學(xué)與生物化學(xué)系主任。2009年至2021年，擔(dān)任 Saul Winstein 有機(jī)化學(xué)講席教授，現(xiàn)為特聘講席教授。Kendall N. Houk從一名實驗有機(jī)化學(xué)家起步，在其職業(yè)生涯中逐漸發(fā)展成為一名理論計算有機(jī)化學(xué)家，并與世界各地研究小組合作。Kendall N. Houk為美國國家科學(xué)院和中國科學(xué)院院士，目前發(fā)表了 1500 多篇論文。
講座摘要
In collaboration with the group of Yi Tang at UCLA, we have explored the use of Alfafold 2 and 3 protein folding predictions and QM and MD studies of mechanism and ligand binding to investigate how novel enzymes catalyze reactions. The Houk and Tang groups have studied a variety of enzymes that catalyze pericyclic reactions. These enzymes include well-studied enzymes such as chorismate mutase and a Diels-Alderase/[6+4]ase, SpnF. The former involves salt bridges, hydrogen-bonding, and pre-organization, while the latter involves primarily hydrophobic effects and preorganization. Two novel pericyclases discovered by the Tang group, BruB and Sdng, will be described here. The former involves a cascade of pericyclic reactions, while the latter involves covalent iminium catalysis. A new selective copper-dependent alkyl group chlorinase, ApnU, will also be discussed.
我們與加州大學(xué)洛杉磯分校（UCLA）的唐奕（Yi Tang）團(tuán)隊合作，利用AlphaFold 2和3的蛋白質(zhì)折疊預(yù)測，以及量子力學(xué)（QM）和分子動力學(xué)（MD）研究，探討新型酶的催化機(jī)制和配體結(jié)合作用。Houk和唐奕團(tuán)隊研究了一系列催化周環(huán)反應(yīng)的酶，包括一些已經(jīng)深入研究的酶，例如莽草酸變位酶和Diels-Alder酶/[6+4]酶SpnF。前者（莽草酸變位酶）的催化機(jī)制涉及鹽橋、氫鍵和預(yù)組織化，而后者（SpnF）則主要依賴于疏水效應(yīng)和預(yù)組織化。這里將描述唐奕團(tuán)隊發(fā)現(xiàn)的兩種新型周環(huán)酶，BruB和Sdng。前者涉及一系列的周環(huán)反應(yīng)，而后者涉及共價亞胺催化。此外，我們還將討論一種新型選擇性的銅依賴烷基氯化酶ApnU。
