Exploring the influence of the protein environment on metal-binding pharmacophores

…, PG Blachly, JA McCammon, SM Cohen

Index: Martin, David P.; Blachly, Patrick G.; Marts, Amy R.; Woodruff, Tessa M.; De Oliveira, Cesar A. F.; McCammon, J. Andrew; Tierney, David L.; Cohen, Seth M. Journal of the American Chemical Society, 2014 , vol. 136, # 14 p. 5400 - 5406

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Citation Number: 6

Abstract

The binding of a series of metal-binding pharmacophores (MBPs) related to the ligand 1- hydroxypyridine-2-(1 H)-thione (1, 2-HOPTO) in the active site of human carbonic anhydrase II (hCAII) has been investigated. The presence and/or position of a single methyl substituent drastically alters inhibitor potency and can result in coordination modes not observed in small-molecule model complexes. It is shown that this unexpected binding mode is the ...