Araújo Edson, Lima Anderson H, Lameira Jerônimo
Institute of Biological Sciences, Federal University of Pará, 66075-110, Belém, PA, Brazil.
Phys Chem Chem Phys. 2017 Aug 16;19(32):21350-21356. doi: 10.1039/c7cp02811c.
Chlorinase SalL halogenate S-adenosyl-l-methionine (SAM) reacts with chloride to generate 5'-chloro-5'-deoxyadenosine and l-methionine through a nucleophilic substitution mechanism. Although it is known that chlorinase enhances the rate of reaction by a factor of 1.2 × 10 fold, it is not entirely clear how this is accomplished. The search for the origin of the catalysis of chlorinase and other enzymes has led to a desolvation hypothesis. In the present work, we have used well defined computational simulations in order to evaluate the origin of the catalytic efficiency of chlorinase. The results demonstrate that the catalytic effect of chlorinase is associated with the fact that Cl is "solvated" by the protein more than by the reference solution reaction, which is not in accordance with proposed catalysis by desolvation. It is found that chlorinase SalL active sites provide electrostatic stabilization of the transition state which is the origin of its catalytic effect.
氯过氧化物酶SalL使S-腺苷-L-甲硫氨酸（SAM）卤化，它通过亲核取代机制与氯离子反应生成5'-氯-5'-脱氧腺苷和L-甲硫氨酸。虽然已知氯过氧化物酶将反应速率提高了1.2×10倍，但目前尚不完全清楚其作用机制。对氯过氧化物酶及其他酶催化作用起源的研究引出了去溶剂化假说。在本研究中，我们使用了定义明确的计算模拟来评估氯过氧化物酶催化效率的起源。结果表明，氯过氧化物酶的催化作用与以下事实有关：与参考溶液反应相比，蛋白质对Cl的“溶剂化”作用更强，这与去溶剂化提出的催化作用不一致。研究发现，氯过氧化物酶SalL的活性位点为过渡态提供了静电稳定作用，这是其催化作用的起源。
