Habib Uzma, Riaz Mahum, Hofmann Matthias
Research Center for Modeling & Simulation (RCMS), National University of Sciences & Technology (NUST), Islamabad 44000, Pakistan.
Anorganisch Chemisches Institüt, Ruprecht-Karls-Universität, Heidelberg 69120, Germany.
ACS Omega. 2021 Mar 2;6(10):6924-6933. doi: 10.1021/acsomega.0c06159. eCollection 2021 Mar 16.
Acetylene hydratase (AH) of is a tungsten (W)-containing iron-sulfur enzyme that catalyzes the transformation of acetylene to acetaldehyde, the exact/true reaction mechanism of which is still in question. Scientists utilized different computational approaches to understand the reaction mechanism of acetylene hydration. Some identified it as a multistep (4-16) process that starts with the displacement of a water molecule present at the active site of AH with acetylene. However, some said that there is no need to displace water with acetylene at the active site of AH. As the reaction mechanism for the conversion of acetylene to acetaldehyde is still controversial and needs to be investigated further, DFT studies were performed on the model complexes derived from the native protein X-ray crystal structure of AH. Based on the computational results, here we are proposing the nucleophilic reaction mechanism where the water (Wat1424) molecule is coordinated to the W center and Asp13 is assumed to be in an anionic form. The Wat1424 molecule is activated by W and then donates one of its protons to the anionic Asp13, forming the W-bound hydroxide and protonated Asp13. The W-bound hydroxide then attacks the C1 atom of acetylene together with the transfer of a proton from Asp13 to its C2 atom, resulting in the formation of a vinyl alcohol intermediate complex. The energy barrier associated with this step is 14.4 kcal/mol. The final, rate-limiting, step corresponds to the tautomerization of the vinyl alcohol intermediate to acetaldehyde via intermolecular assistance of two water molecules, associated with an energy barrier of 18.9 kcal/mol. Also, the influence of the metal on the hydration of acetylene is studied when W is replaced with Mo.
乙炔水合酶（AH）是一种含钨（W）的铁硫酶，可催化乙炔转化为乙醛，其确切的反应机制仍存在疑问。科学家们采用了不同的计算方法来理解乙炔水合反应的机制。一些人认为这是一个多步（4-16步）过程，始于乙炔取代AH活性位点上的水分子。然而，也有人表示在AH的活性位点无需用乙炔取代水。由于乙炔转化为乙醛的反应机制仍存在争议，需要进一步研究，因此对源自AH天然蛋白质X射线晶体结构的模型配合物进行了密度泛函理论（DFT）研究。基于计算结果，我们在此提出亲核反应机制，即水分子（Wat1424）与W中心配位，且假定天冬氨酸13（Asp13）呈阴离子形式。Wat1424分子被W激活，然后将其一个质子捐赠给阴离子形式的Asp13，形成与W结合的氢氧化物和质子化的Asp13。与W结合的氢氧化物随后与一个质子从Asp13转移至乙炔的C2原子一起攻击乙炔的C1原子，导致形成乙烯醇中间体配合物。与该步骤相关的能垒为14.4千卡/摩尔。最后一步也是限速步骤，是乙烯醇中间体通过两个水分子的分子间协助互变异构为乙醛，相关能垒为18.9千卡/摩尔。此外，还研究了用钼（Mo）取代W时金属对乙炔水合作用的影响。
