4D1N

Structure of human nNOS heme domain with L-Arg bound

4D1N の概要

• エントリーDOI: 10.2210/pdb4d1n/pdb
• 関連するPDBエントリー: 4D1O 4D1P
• 分子名称: NITRIC OXIDE SYNTHASE, BRAIN, ARGININE, PROTOPORPHYRIN IX CONTAINING FE, ... (7 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cell membrane, sarcolemma; Peripheral membrane protein: P29475
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 199528.51

構造登録者

Li, H.,Poulos, T.L. (登録日: 2014-05-02, 公開日: 2014-10-15, 最終更新日: 2023-12-20)

主引用文献

Li, H.,Jamal, J.,Plaza, C.,Pineda, S.H.,Chreifi, G.,Jing, Q.,Cinelli, M.A.,Silverman, R.B.,Poulos, T.L.
Structures of Human Constitutive Nitric Oxide Synthases
Acta Crystallogr.,Sect.D, 70:2667-, 2014

PubMed Abstract: Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution.

PubMed: 25286850
DOI: 10.1107/S1399004714017064

実験手法

X-RAY DIFFRACTION (2.03 Å)