Electrostatic fields near the active site of human aldose reductase: 2. New inhibitors and complications caused by hydrogen bonds.

ABSTRACT: Vibrational Stark effect spectroscopy was used to measure electrostatic fields in the hydrophobic region of the active site of human aldose reductase (hALR2). A new nitrile-containing inhibitor was designed and synthesized, and the X-ray structure of its complex, along with cofactor NADP(+), with wild-type hALR2 was determined at 1.3 Å resolution. The nitrile is found to be in the proximity of T113, consistent with a hydrogen bond interaction. Two vibrational absorption peaks were observed at room temperature in the nitrile region when the inhibitor binds to wild-type hALR2, indicating that the nitrile probe experiences two different microenvironments, and these could be empirically separated into a hydrogen-bonded and non-hydrogen-bonded population by comparison with the T113A mutant, in

SUBMITTER: Xu L 

PROVIDER: S-EPMC3183354 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature