1tll
From Proteopedia
(New page: 200px<br /><applet load="1tll" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tll, resolution 2.30Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1tll.gif|left|200px]]<br /><applet load="1tll" size=" | + | [[Image:1tll.gif|left|200px]]<br /><applet load="1tll" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1tll, resolution 2.30Å" /> | caption="1tll, resolution 2.30Å" /> | ||
'''CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE REDUCTASE MODULE AT 2.3 A RESOLUTION.'''<br /> | '''CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE REDUCTASE MODULE AT 2.3 A RESOLUTION.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Three nitric-oxide synthase (NOS) isozymes play crucial, but distinct, roles in neurotransmission, vascular homeostasis, and host defense, by | + | 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== | ==About this Structure== | ||
| - | 1TLL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with SO3, FMN, FAD and NAP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] Full crystallographic information is available from [http:// | + | 1TLL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=SO3:'>SO3</scene>, <scene name='pdbligand=FMN:'>FMN</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=NAP:'>NAP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TLL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bruns, C | + | [[Category: Bruns, C M.]] |
[[Category: Gachhui, R.]] | [[Category: Gachhui, R.]] | ||
| - | [[Category: Garcin, E | + | [[Category: Garcin, E D.]] |
| - | [[Category: Getzoff, E | + | [[Category: Getzoff, E D.]] |
| - | [[Category: Hosfield, D | + | [[Category: Hosfield, D J.]] |
| - | [[Category: Lloyd, S | + | [[Category: Lloyd, S J.]] |
| - | [[Category: Stuehr, D | + | [[Category: Stuehr, D J.]] |
| - | [[Category: Tainer, J | + | [[Category: Tainer, J A.]] |
[[Category: Tiso, M.]] | [[Category: Tiso, M.]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: reductase module]] | [[Category: reductase module]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:14:49 2008'' |
Revision as of 13:14, 21 February 2008
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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 with , , and as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 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 Thu Feb 21 15:14:49 2008
Categories: Nitric-oxide synthase | Rattus norvegicus | Single protein | Bruns, C M. | Gachhui, R. | Garcin, E D. | Getzoff, E D. | Hosfield, D J. | Lloyd, S J. | Stuehr, D J. | Tainer, J A. | Tiso, M. | FAD | FMN | NAP | SO3 | Fad | Fmn | Nadp+ | Reductase module
