Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

1RS6

Rat neuronal NOS heme domain with D-lysine-D-nitroarginine amide bound

Summary for 1RS6
Entry DOI10.2210/pdb1rs6/pdb
Related1RS7 1RS8 1RS9
DescriptorNitric-oxide synthase, brain, D-MANNITOL, ACETATE ION, ... (8 entities in total)
Functional Keywordsnitric oxide synthase, oxidoreductase, heme-enzyme
Biological sourceRattus norvegicus (Norway rat)
Cellular locationCell membrane, sarcolemma; Peripheral membrane protein (By similarity): P29476
Total number of polymer chains2
Total formula weight100471.07
Authors
Flinspach, M.,Li, H.,Jamal, J.,Yang, W.,Huang, H.,Silverman, R.B.,Poulos, T.L. (deposition date: 2003-12-09, release date: 2004-05-18, Last modification date: 2024-02-14)
Primary citationFlinspach, M.,Li, H.,Jamal, J.,Yang, W.,Huang, H.,Silverman, R.B.,Poulos, T.L.
Structures of the Neuronal and Endothelial Nitric Oxide Synthase Heme Domain with d-Nitroarginine-Containing Dipeptide Inhibitors Bound.
Biochemistry, 43:5181-5187, 2004
Cited by
PubMed Abstract: In a continuing effort to unravel the structural basis for isoform-selective inhibition of nitric oxide synthase (NOS) by various inhibitors, we have determined the crystal structures of the nNOS and eNOS heme domain bound with two D-nitroarginine-containing dipeptide inhibitors, D-Lys-D-Arg(NO)2-NH(2) and D-Phe-D-Arg(NO)2-NH(2). These two dipeptide inhibitors exhibit similar binding modes in the two constitutive NOS isozymes, which is consistent with the similar binding affinities for the two isoforms as determined by K(i) measurements. The D-nitroarginine-containing dipeptide inhibitors are not distinguished by the amino acid difference between nNOS and eNOS (Asp 597 and Asn 368, respectively) which is key in controlling isoform selection for nNOS over eNOS observed for the L-nitroarginine-containing dipeptide inhibitors reported previously [Flinspach, M., et al. (2004) Nat. Struct. Mol. Biol. 11, 54-59]. The lack of a free alpha-amino group on the D-nitroarginine moiety makes the dipeptide inhibitor steer away from the amino acid binding pocket near the active site. This allows the inhibitor to extend into the solvent-accessible channel farther away from the active site, which enables the inhibitors to explore new isoform-specific enzyme-inhibitor interactions. This might be the structural basis for why these D-nitroarginine-containing inhibitors are selective for nNOS (or eNOS) over iNOS.
PubMed: 15122883
DOI: 10.1021/bi0361867
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.95 Å)
Structure validation

238268

數據於2025-07-02公開中

PDB statisticsPDBj update infoContact PDBjnumon