1lzz | pdb_00001lzz
Rat neuronal NOS heme domain with N-isopropyl-N'-hydroxyguanidine bound
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| 1lzz, resolution 2.05Å | |||||||||||||
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| Ligands: | ACT, ZN, HEM, H4B and IHG | ||||||||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.
About this Structure
1LZZ is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
The novel binding mode of N-alkyl-N'-hydroxyguanidine to neuronal nitric oxide synthase provides mechanistic insights into NO biosynthesis., Li H, Shimizu H, Flinspach M, Jamal J, Yang W, Xian M, Cai T, Wen EZ, Jia Q, Wang PG, Poulos TL, Biochemistry. 2002 Nov 26;41(47):13868-75. PMID:12437343
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