1NIW

Crystal structure of endothelial nitric oxide synthase peptide bound to calmodulin

Summary for 1NIW

• Entry DOI: 10.2210/pdb1niw/pdb
• Descriptor: calmodulin, Nitric-oxide synthase, endothelial, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: nitric oxide, calcium-binding protein, nos, signaling protein-oxidoreductase complex, signaling protein/oxidoreductase
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62161; Cell membrane: P29474
• Total number of polymer chains: 8
• Total formula weight: 78293.75

Authors

Aoyagi, M.,Arvai, A.S.,Tainer, J.A.,Getzoff, E.D. (deposition date: 2002-12-26, release date: 2003-02-18, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.05 Å)