1tll
From Proteopedia
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| , resolution 2.30Å | |||||||
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| Ligands: | , , , | ||||||
| Gene: | NOS1, BNOS (Rattus norvegicus) | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Related: | 1F20
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE REDUCTASE MODULE AT 2.3 A RESOLUTION.
Overview
Three nitric-oxide synthase (NOS) isozymes play crucial, but distinct, roles in neurotransmission, vascular homeostasis, and host defense, by catalyzing Ca(2+)/calmodulin-triggered NO synthesis. Here, we address current questions regarding NOS activity and regulation by combining mutagenesis and biochemistry with crystal structure determination of a fully assembled, electron-supplying, neuronal NOS reductase dimer. By integrating these results, we structurally elucidate the unique mechanisms for isozyme-specific regulation of electron transfer in NOS. Our discovery of the autoinhibitory helix, its placement between domains, and striking similarities with canonical calmodulin-binding motifs, support new mechanisms for NOS inhibition. NADPH, isozyme-specific residue Arg(1400), and the C-terminal tail synergistically repress NOS activity by locking the FMN binding domain in an electron-accepting position. Our analyses suggest that calmodulin binding or C-terminal tail phosphorylation frees a large scale swinging motion of the entire FMN domain to deliver electrons to the catalytic module in the holoenzyme.
About this Structure
1TLL is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural basis for isozyme-specific regulation of electron transfer in nitric-oxide synthase., Garcin ED, Bruns CM, Lloyd SJ, Hosfield DJ, Tiso M, Gachhui R, Stuehr DJ, Tainer JA, Getzoff ED, J Biol Chem. 2004 Sep 3;279(36):37918-27. Epub 2004 Jun 17. PMID:15208315
Page seeded by OCA on Sun Mar 30 23:57:49 2008
