1LZX

Rat neuronal NOS heme domain with NG-hydroxy-L-arginine bound

Summary for 1LZX

• Entry DOI: 10.2210/pdb1lzx/pdb
• Related: 1LZZ 1M00
• Descriptor: Nitric-oxide synthase, ACETATE ION, ZINC ION, ... (7 entities in total)
• Functional Keywords: nitric oxide synthase, oxydoreductase, heme-enzyme, oxidoreductase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cell membrane, sarcolemma; Peripheral membrane protein (By similarity): P29476
• Total number of polymer chains: 2
• Total formula weight: 99389.79

Authors

Li, H.,Shimizu, H.,Flinspach, M.,Jamal, J.,Yang, W.,Xian, M.,Cai, T.,Wen, E.Z.,Jia, Q.,Wang, P.G.,Poulos, T.L. (deposition date: 2002-06-11, release date: 2002-11-27, Last modification date: 2024-02-14)

Primary citation

Li, H.,Shimizu, H.,Flinspach, M.,Jamal, J.,Yang, W.,Xian, M.,Cai, T.,Wen, E.Z.,Jia, Q.,Wang, P.G.,Poulos, T.L.
The Novel Binding Mode of N-Alkyl-N'-Hydroxyguanidine to Neuronal Nitric Oxide Synthase Provides Mechanistic Insights into NO Biosynthesis
Biochemistry, 41:13868-13875, 2002

PubMed 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.

PubMed: 12437343
DOI: 10.1021/bi020417c

Experimental method

X-RAY DIFFRACTION (2 Å)