Journal article
The novel binding mode of N-alkyl-N'-hydroxyguanidine to neuronal nitric oxide synthase provides mechanistic insights into NO biosynthesis
Biochemistry (Easton), Vol.41(47), pp.13868-13875
11/26/2002
Handle:
https://hdl.handle.net/2376/104653
PMID: 12437343
Abstract
A series of N-alkyl-N'-hydroxyguanidine compounds have recently been characterized as non-amino acid substrates for all three nitric oxide synthase (NOS) isoforms which mimic NO formation from N(omega)-hydroxy-L-arginine. Crystal structures of the nNOS heme domain complexed with either N-isopropyl-N'-hydroxyguanidine or N-butyl-N'-hydroxyguanidine reveal two different binding modes in the substrate binding pocket. The binding mode of the latter is consistent with that observed for the substrate N(omega)-hydroxy-L-arginine bound in the nNOS active site. However, the former binds to nNOS in an unexpected fashion, thus providing new insights into the mechanism on how the hydroxyguanidine moiety leads to NO formation. Structural features of substrate binding support the view that the OH-substituted guanidine nitrogen, instead of the hydroxyl oxygen, is the source of hydrogen supplied to the active ferric-superoxy species for the second step of the NOS catalytic reaction.
Metrics
8 Record Views
Details
- Title
- The novel binding mode of N-alkyl-N'-hydroxyguanidine to neuronal nitric oxide synthase provides mechanistic insights into NO biosynthesis
- Creators
- Huiying Li - Department of Molecular Biology and Biochemistry and Program in Macromolecular Structures, University of California, Irvine, California 92697, USAHideaki ShimizuMack FlinspachJoumana JamalWeiping YangMing XianTingwei CaiEdward Zhong WenQiang JiaPeng George WangThomas L Poulos
- Publication Details
- Biochemistry (Easton), Vol.41(47), pp.13868-13875
- Academic Unit
- Chemistry, Department of
- Publisher
- United States
- Grant note
- GM57353 / NIGMS NIH HHS GM54074 / NIGMS NIH HHS
- Identifiers
- 99900546617001842
- Language
- English
- Resource Type
- Journal article