How does catalase release nitric oxide? A computational structure-activity relationship study.

ABSTRACT: Hydroxyurea (HU) is the only FDA approved medication for treating sickle cell disease in adults. The primary mechanism of action is pharmacological elevation of nitric oxide (NO) levels which induces propagation of fetal hemoglobin. HU is known to undergo redox reactions with heme based enzymes like hemoglobin and catalase to produce NO. However, specific details about the HU based NO release remain unknown. Experimental studies indicate that interaction of HU with human catalase compound I produces NO. Presently, we combine flexible receptor-flexible substrate induced fit docking (IFD) with energy decomposition analyses to examine the atomic level details of a possible key step in the clinical conversion of HU to NO. Substrate binding modes of nine HU analogs with catalase compound I were

SUBMITTER: Vankayala SL 

PROVIDER: S-EPMC3893047 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature