A Raman-active competitive inhibitor of OMP decarboxylase

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• 作者：Brian P. Callahan ; Alasdair F. Bell ; Peter J. Tonge and Richard Wolfenden
• 关键词：OMP decarboxylase ; Ground state destabilization ; Raman spectroscopy ; Catalysis ; Decarboxylation ; Nitrile group ; ODCase
• 刊名：Bioorganic Chemistry
• 出版年：2006
• 期刊代码：117_00452068
• 类别：ch
• 出版时间：April 2006
• 卷：34
• 期：2
• 页码：59-65
• 文件大小：156 K

摘要

6-Cyanouridine 5′-phosphate was shown to act as a competitive inhibitor of yeast OMP decarboxylase, with a K_i value of 1.1 × 10⁻⁵ M. Upon binding by the active site of yeast OMP decarboxylase (EC 4.1.1.23), the Raman stretching frequency of the nitrile group of 6-cyanouridine 5′-phosphate decreases from 2240 to 2225 cm⁻¹. Based on the behavior of a model compound, 6-cyano-1,3-dimethyluracil, and on vibrational calculations, the observed change in stretching frequency is attributed to desolvation of the ligand, and distortion of the ligand in which the nitrile group moves out of the plane of the pyrimidine ring. Similar distortions may play a role in substrate activation by OMP decarboxylase, contributing to the catalytic process.