疏水性异羟肟酸的结合增强了过氧化物酶在非水硫氧化反应中的立体选择性。

Binding of hydrophobic hydroxamic acids enhances peroxidase's stereoselectivity in nonaqueous sulfoxidations.

作者信息

Das Prasanta Kumar, Caaveiro Jose M M, Luque Susana, Klibanov Alexander M

机构信息

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

出版信息

J Am Chem Soc. 2002 Feb 6;124(5):782-7. doi: 10.1021/ja012075o.

DOI:10.1021/ja012075o

PMID:11817954

Abstract

Horseradish peroxidase exhibits a meager stereoselectivity (E) in the sulfoxidation of thioanisole (1a) in 99.8% (v/v) methanol. The E value, however, is greatly enhanced when the enzyme forms a complex with benzohydroxamic acid (2a). These findings are rationalized by means of molecular dynamics simulations and energy minimization which correctly explain (i) why the free enzyme is not stereoselective, (ii) why 2a inhibits peroxidase-catalyzed sulfoxidation of 1a but the enzymatic formation of one enantiomer of the sulfoxide product is inhibited much more than that of the other, thereby raising peroxidase's E, and (iii) why in the presence of 2a the enzyme favors production of the S sulfoxide of 1a. The generality of the observed ligand-induced stereoselectivity enhancement is demonstrated with other hydrophobic hydroxamic acids, as well as with additional thioether substrates.

摘要

辣根过氧化物酶在99.8%（v/v）甲醇中对苯甲硫醚（1a）进行硫氧化反应时表现出微弱的立体选择性（E）。然而，当该酶与苯甲羟肟酸（2a）形成复合物时，E值会大大提高。通过分子动力学模拟和能量最小化对这些发现进行了合理化解释，这些解释正确地说明了：（i）为什么游离酶没有立体选择性；（ii）为什么2a抑制过氧化物酶催化的1a的硫氧化反应，但硫氧化物产物的一种对映体的酶促形成受到的抑制比另一种对映体大得多，从而提高了过氧化物酶的E值；（iii）为什么在2a存在的情况下，该酶有利于生成1a的S-亚砜。其他疏水性羟肟酸以及其他硫醚底物也证明了观察到的配体诱导的立体选择性增强的普遍性。