1DWX

MURINE INDUCIBLE NITRIC OXIDE SYNTHASE OXYGENASE DIMER N-hydroxyarginine and tetrahydrobiopterin

1DWX の概要

• エントリーDOI: 10.2210/pdb1dwx/pdb
• 関連するPDBエントリー: 1DWV 1DWW 1NOC 1NOD 1NOS 1QOM 2NOD 2NOS 3NOD
• 分子名称: NITRIC OXIDE SYNTHASE, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (6 entities in total)
• 機能のキーワード: oxidoreductase transferase complex, complex (oxidoreductase-transferase), nitric oxide monooxygenase, heme, dimer, intermediate, pterin, h4b, tetrahydrobiopterin, oxidoreductase-transferase complex, oxidoreductase/transferase
• 由来する生物種: MUS MUSCULUS (MOUSE)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99444.52

構造登録者

Crane, B.R.,Arvai, A.S.,Getzoff, E.D.,Stuehr, D.J.,Tainer, J.A. (登録日: 1999-12-14, 公開日: 2000-02-06, 最終更新日: 2024-05-08)

主引用文献

Crane, B.R.,Arvai, A.S.,Ghosh, S.,Getzoff, E.D.,Stuehr, D.J.,Tainer, J.A.
Structures of the N(Omega)-Hydroxy-L-Arginine Complex of Inducible Nitric Oxide Synthase Oxygenase Dimer with Active Andinactive Pterins
Biochemistry, 39:4608-, 2000

PubMed Abstract: Nitric oxide synthases (NOSs) catalyze two mechanistically distinct, tetrahydrobiopterin (H(4)B)-dependent, heme-based oxidations that first convert L-arginine (L-Arg) to N(omega)-hydroxy-L-arginine (NHA) and then NHA to L-citrulline and nitric oxide. Structures of the murine inducible NOS oxygenase domain (iNOS(ox)) complexed with NHA indicate that NHA and L-Arg both bind with the same conformation adjacent to the heme iron and neither interacts directly with it nor with H(4)B. Steric restriction of dioxygen binding to the heme in the NHA complex suggests either small conformational adjustments in the ternary complex or a concerted reaction of dioxygen with NHA and the heme iron. Interactions of the NHA hydroxyl with active center beta-structure and the heme ring polarize and distort the hydroxyguanidinium to increase substrate reactivity. Steric constraints in the active center rule against superoxo-iron accepting a hydrogen atom from the NHA hydroxyl in their initial reaction, but support an Fe(III)-peroxo-NHA radical conjugate as an intermediate. However, our structures do not exclude an oxo-iron intermediate participating in either L-Arg or NHA oxidation. Identical binding modes for active H(4)B, the inactive quinonoid-dihydrobiopterin (q-H(2)B), and inactive 4-amino-H(4)B indicate that conformational differences cannot explain pterin inactivity. Different redox and/or protonation states of q-H(2)B and 4-amino-H(4)B relative to H(4)B likely affect their ability to electronically influence the heme and/or undergo redox reactions during NOS catalysis. On the basis of these structures, we propose a testable mechanism where neutral H(4)B transfers both an electron and a 3,4-amide proton to the heme during the first step of NO synthesis.

PubMed: 10769116
DOI: 10.1021/BI992409A

実験手法

X-RAY DIFFRACTION (2.6 Å)