1NIW: Crystal Structure Of Endothelial Nitric Oxide Synthase Peptide Bound To Calmodulin

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.
PDB ID: 1NIWDownload
MMDB ID: 22130
PDB Deposition Date: 2002/12/26
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.05  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 1NIW: dimeric; determined by author and by software (PISA)
Molecular Components in 1NIW
Label Count Molecule
Proteins (2 molecules)
Molecule annotation
Nitric-oxide Synthase, Endothelial(Gene symbol: NOS3)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB