1tll: Difference between revisions

Line 1:

[[Image:1tll.gif|left|200px]]<br /><applet load="1tll" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1tll.gif|left|200px]]<br /><applet load="1tll" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1tll, resolution 2.30Å" />

'''CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE REDUCTASE MODULE AT 2.3 A RESOLUTION.'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1TLL OCA].

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==

Line 14:

[[Category: Rattus norvegicus]]

[[Category: Single protein]]

[[Category: Bruns, C.M.]]

[[Category: Bruns, C M.]]

[[Category: Gachhui, R.]]

[[Category: Garcin, E.D.]]

[[Category: Garcin, E D.]]

[[Category: Getzoff, E.D.]]

[[Category: Getzoff, E D.]]

[[Category: Hosfield, D.J.]]

[[Category: Hosfield, D J.]]

[[Category: Lloyd, S.J.]]

[[Category: Lloyd, S J.]]

[[Category: Stuehr, D.J.]]

[[Category: Stuehr, D J.]]

[[Category: Tainer, J.A.]]

[[Category: Tainer, J A.]]

[[Category: Tiso, M.]]

[[Category: FAD]]

Line 33:

[[Category: reductase module]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 03:23:~~04 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:14:49 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:1tll.gif|left|200px]]<br /><applet load="1tll" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1tll.gif|left|200px]]<br /><applet load="1tll" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1tll, resolution 2.30&Aring;" />
 '''CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE REDUCTASE MODULE AT 2.3 A RESOLUTION.'''<br />
 ==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.
+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==
-TLL 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TLL OCA].
+TLL 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==
@@ Line 14: / Line 14: @@
 [[Category: Rattus norvegicus]]
 [[Category: Single protein]]
-[[Category: Bruns, C.M.]]
+[[Category: Bruns, C M.]]
 [[Category: Gachhui, R.]]
-[[Category: Garcin, E.D.]]
+[[Category: Garcin, E D.]]
-[[Category: Getzoff, E.D.]]
+[[Category: Getzoff, E D.]]
-[[Category: Hosfield, D.J.]]
+[[Category: Hosfield, D J.]]
-[[Category: Lloyd, S.J.]]
+[[Category: Lloyd, S J.]]
-[[Category: Stuehr, D.J.]]
+[[Category: Stuehr, D J.]]
-[[Category: Tainer, J.A.]]
+[[Category: Tainer, J A.]]
 [[Category: Tiso, M.]]
 [[Category: FAD]]
@@ Line 33: / Line 33: @@
 [[Category: reductase module]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:23:04 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:14:49 2008''