1p6k: Difference between revisions

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[[Image:1p6k.png|left|200px]]


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==Rat neuronal NOS D597N mutant heme domain with L-N(omega)-nitroarginine-2,4-L-diaminobutyric amide bound==
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<StructureSection load='1p6k' size='340' side='right'caption='[[1p6k]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1p6k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P6K FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DP1:L-N(OMEGA)-NITROARGININE-2,4-L-DIAMINOBUTYRIC+AMIDE'>DP1</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MTL:D-MANNITOL'>MTL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
{{STRUCTURE_1p6k|  PDB=1p6k  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p6k OCA], [https://pdbe.org/1p6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p6k RCSB], [https://www.ebi.ac.uk/pdbsum/1p6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p6k ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NOS1_RAT NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
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    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1p6k ConSurf].
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== Publication Abstract from PubMed ==
Three nitric oxide synthase (NOS) isoforms, eNOS, nNOS and iNOS, generate nitric oxide (NO) crucial to the cardiovascular, nervous and host defense systems, respectively. Development of isoform-selective NOS inhibitors is of considerable therapeutic importance. Crystal structures of nNOS-selective dipeptide inhibitors in complex with both nNOS and eNOS were solved and the inhibitors were found to adopt a curled conformation in nNOS but an extended conformation in eNOS. We hypothesized that a single-residue difference in the active site, Asp597 (nNOS) versus Asn368 (eNOS), is responsible for the favored binding in nNOS. In the D597N nNOS mutant crystal structure, a bound inhibitor switches to the extended conformation and its inhibition of nNOS decreases &gt;200-fold. Therefore, a single-residue difference is responsible for more than two orders of magnitude selectivity in inhibition of nNOS over eNOS by L-N(omega)-nitroarginine-containing dipeptide inhibitors.


===Rat neuronal NOS D597N mutant heme domain with L-N(omega)-nitroarginine-2,4-L-diaminobutyric amide bound===
Structural basis for dipeptide amide isoform-selective inhibition of neuronal nitric oxide synthase.,Flinspach ML, Li H, Jamal J, Yang W, Huang H, Hah JM, Gomez-Vidal JA, Litzinger EA, Silverman RB, Poulos TL Nat Struct Mol Biol. 2004 Jan;11(1):54-9. Epub 2003 Dec 29. PMID:14718923<ref>PMID:14718923</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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{{ABSTRACT_PUBMED_14718923}}
 
==About this Structure==
[[1p6k]] is a 2 chain structure of [[Nitric Oxide Synthase (Part II)]] and [[Nitric oxide synthase]] with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P6K OCA].


==See Also==
==See Also==
*[[Nitric Oxide Synthase (Part II)]]
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
*[[Nitric oxide synthase]]
== References ==
 
<references/>
==Reference==
__TOC__
<ref group="xtra">PMID:014718923</ref><references group="xtra"/>
</StructureSection>
[[Category: Nitric-oxide synthase]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Flinspach, M L.]]
[[Category: Flinspach ML]]
[[Category: Gomez-Vidal, J A.]]
[[Category: Gomez-Vidal JA]]
[[Category: Hah, J M.]]
[[Category: Hah J-M]]
[[Category: Huang, H.]]
[[Category: Huang H]]
[[Category: Jamal, J.]]
[[Category: Jamal J]]
[[Category: Li, H.]]
[[Category: Li H]]
[[Category: Litzinger, E A.]]
[[Category: Litzinger EA]]
[[Category: Poulos, T L.]]
[[Category: Poulos TL]]
[[Category: Silverman, R B.]]
[[Category: Silverman RB]]
[[Category: Yang, W.]]
[[Category: Yang W]]
[[Category: Heme-enzyme]]
[[Category: Nitric oxide synthase]]
[[Category: Oxidoreductase]]