1LZZ

Rat neuronal NOS heme domain with N-isopropyl-N'-hydroxyguanidine bound

1LZZ の概要

• エントリーDOI: 10.2210/pdb1lzz/pdb
• 関連するPDBエントリー: 1LZZ 1M00
• 分子名称: Nitric-oxide synthase, ACETATE ION, ZINC ION, ... (7 entities in total)
• 機能のキーワード: nitric oxide synthase, oxydoreductase, heme-enzyme, oxidoreductase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cell membrane, sarcolemma; Peripheral membrane protein (By similarity): P29476
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99243.70

構造登録者

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. (登録日: 2002-06-11, 公開日: 2002-11-27, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.05 Å)