1Q2O

Bovine endothelial nitric oxide synthase N368D mutant heme domain dimer with L-N(omega)-nitroarginine-2,4-L-diaminobutyramide bound

1Q2O の概要

• エントリーDOI: 10.2210/pdb1q2o/pdb
• 関連するPDBエントリー: 1P6H 1P6I 1P6J 1P6K 1P6L 1P6M 1P6N
• 分子名称: Nitric-oxide synthase, endothelial, CACODYLATE ION, ACETATE ION, ... (9 entities in total)
• 機能のキーワード: oxidoreductase, endothelial nitric oxide synthase, enos, nos iii, heme protein
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Cell membrane: P29473
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96703.82

構造登録者

Flinspach, M.L.,Li, H.,Jamal, J.,Yang, W.,Huang, H.,Hah, J.M.,Gomez-Vidal, J.A.,Litzinger, E.A.,Silverman, R.B.,Poulos, T.L. (登録日: 2003-07-25, 公開日: 2004-01-13, 最終更新日: 2024-04-03)

主引用文献

Flinspach, M.L.,Li, H.,Jamal, J.,Yang, W.,Huang, H.,Hah, J.M.,Gomez-Vidal, J.A.,Litzinger, E.A.,Silverman, R.B.,Poulos, T.L.
Structural basis for dipeptide amide isoform-selective inhibition of neuronal nitric oxide synthase.
Nat.Struct.Mol.Biol., 11:54-59, 2004

PubMed Abstract: Three nitric oxide synthase (NOS) isoforms, eNOS, nNOS and iNOS, generate nitric oxide (NO) crucial to the cardiovascular, nervous and host defense systems, respectively. Development of isoform-selective NOS inhibitors is of considerable therapeutic importance. Crystal structures of nNOS-selective dipeptide inhibitors in complex with both nNOS and eNOS were solved and the inhibitors were found to adopt a curled conformation in nNOS but an extended conformation in eNOS. We hypothesized that a single-residue difference in the active site, Asp597 (nNOS) versus Asn368 (eNOS), is responsible for the favored binding in nNOS. In the D597N nNOS mutant crystal structure, a bound inhibitor switches to the extended conformation and its inhibition of nNOS decreases >200-fold. Therefore, a single-residue difference is responsible for more than two orders of magnitude selectivity in inhibition of nNOS over eNOS by L-N(omega)-nitroarginine-containing dipeptide inhibitors.

PubMed: 14718923
DOI: 10.1038/nsmb704

実験手法

X-RAY DIFFRACTION (1.74 Å)