1NIW

Crystal structure of endothelial nitric oxide synthase peptide bound to calmodulin

1NIW の概要

• エントリーDOI: 10.2210/pdb1niw/pdb
• 分子名称: calmodulin, Nitric-oxide synthase, endothelial, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: nitric oxide, calcium-binding protein, nos, signaling protein-oxidoreductase complex, signaling protein/oxidoreductase
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, spindle: P62161; Cell membrane: P29474
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 78293.75

構造登録者

Aoyagi, M.,Arvai, A.S.,Tainer, J.A.,Getzoff, E.D. (登録日: 2002-12-26, 公開日: 2003-02-18, 最終更新日: 2024-11-13)

主引用文献

Aoyagi, M.,Arvai, A.S.,Tainer, J.A.,Getzoff, E.D.
Structural basis for endothelial nitric oxide synthase binding to calmodulin
Embo J., 22:766-775, 2003

PubMed Abstract: The enzyme nitric oxide synthase (NOS) is exquisitely regulated in vivo by the Ca(2+) sensor protein calmodulin (CaM) to control production of NO, a key signaling molecule and cytotoxin. The differential activation of NOS isozymes by CaM has remained enigmatic, despite extensive research. Here, the crystallographic structure of Ca(2+)-loaded CaM bound to a 20 residue peptide comprising the endothelial NOS (eNOS) CaM-binding region establishes their individual conformations and intermolecular interactions, and suggests the basis for isozyme-specific differences. The alpha-helical eNOS peptide binds in an antiparallel orientation to CaM through extensive hydrophobic interactions. Unique NOS interactions occur with: (i). the CaM flexible central linker, explaining its importance in NOS activation; and (ii). the CaM C-terminus, explaining the NOS-specific requirement for a bulky, hydrophobic residue at position 144. This binding mode expands mechanisms for CaM-mediated activation, explains eNOS deactivation by Thr495 phosphorylation, and implicates specific hydrophobic residues in the Ca(2+) independence of inducible NOS.

PubMed: 12574113
DOI: 10.1093/emboj/cdg078

実験手法

X-RAY DIFFRACTION (2.05 Å)