1zzr: Difference between revisions
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==Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound== | ==Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound== | ||
<StructureSection load='1zzr' size='340' side='right' caption='[[1zzr]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='1zzr' size='340' side='right'caption='[[1zzr]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1zzr]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1zzr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZZR FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DP9:L-N(OMEGA)-NITROARGININE-(4R)-AMINO-L-PROLINE+AMIDE'>DP9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=TFA:TRIFLUOROACETIC+ACID'>TFA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DP9:L-N(OMEGA)-NITROARGININE-(4R)-AMINO-L-PROLINE+AMIDE'>DP9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=TFA:TRIFLUOROACETIC+ACID'>TFA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1p6j|1p6j]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1p6j|1p6j]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zzr OCA], [https://pdbe.org/1zzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zzr RCSB], [https://www.ebi.ac.uk/pdbsum/1zzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zzr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</div> | </div> | ||
<div class="pdbe-citations 1zzr" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1zzr" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | [[Category: Buffalo rat]] | ||
[[Category: Large Structures]] | |||
[[Category: Flinspach, M L]] | [[Category: Flinspach, M L]] | ||
[[Category: Gomez-Vidal, J A]] | [[Category: Gomez-Vidal, J A]] | ||
Revision as of 11:21, 27 January 2021
Rat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide boundRat nNOS D597N/M336V double mutant with L-N(omega)-Nitroarginine-(4R)-amino-L-proline amide bound
Structural highlights
Function[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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA series of L-nitroarginine-based dipeptide inhibitors are highly selective for neuronal nitric oxide synthase (nNOS) over the endothelial isoform (eNOS). Crystal structures of these dipeptides bound to both isoforms revealed two different conformations, curled in nNOS and extended in eNOS, corresponding to higher and lower binding affinity to the two isoforms, respectively. In previous studies we found that the primary reason for selectivity is that Asp597 in nNOS, which is Asn368 in eNOS, provides greater electrostatic stabilization in the inhibitor complex. While this is the case for smaller dipeptide inhibitors, electrostatic stabilization may no longer be the sole determinant for isoform selectivity with bulkier dipeptide inhibitors. Another residue farther away from the active site, Met336 in nNOS (Val106 in eNOS), is in contact with bulkier dipeptide inhibitors. Double mutants were made to exchange the D597/M336 pair in nNOS with N368/V106 in eNOS. Here we report crystal structures and inhibition constants for bulkier dipeptide inhibitors bound to nNOS and eNOS that illustrate the important role played by residues near the entry to the active site in isoform selective inhibition. Exploring the binding conformations of bulkier dipeptide amide inhibitors in constitutive nitric oxide synthases.,Li H, Flinspach ML, Igarashi J, Jamal J, Yang W, Gomez-Vidal JA, Litzinger EA, Huang H, Erdal EP, Silverman RB, Poulos TL Biochemistry. 2005 Nov 22;44(46):15222-9. PMID:16285725[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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