4d1n: Difference between revisions
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==Structure of human nNOS heme domain with L-Arg bound== | |||
<StructureSection load='4d1n' size='340' side='right'caption='[[4d1n]], [[Resolution|resolution]] 2.03Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4d1n]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D1N FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.03Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARG:ARGININE'>ARG</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=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4d1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d1n OCA], [https://pdbe.org/4d1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d1n RCSB], [https://www.ebi.ac.uk/pdbsum/4d1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d1n ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NOS1_HUMAN NOS1_HUMAN] 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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 A resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 A resolution. | |||
Structures of human constitutive nitric oxide synthases.,Li H, Jamal J, Plaza C, Pineda SH, Chreifi G, Jing Q, Cinelli MA, Silverman RB, Poulos TL Acta Crystallogr D Biol Crystallogr. 2014 Oct 1;70(Pt 10):2667-74. doi:, 10.1107/S1399004714017064. Epub 2014 Sep 27. PMID:25286850<ref>PMID:25286850</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4d1n" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Li H]] | |||
[[Category: Poulos TL]] | |||
Latest revision as of 15:19, 20 December 2023
Structure of human nNOS heme domain with L-Arg boundStructure of human nNOS heme domain with L-Arg bound
Structural highlights
FunctionNOS1_HUMAN 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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Publication Abstract from PubMedMammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 A resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 A resolution. Structures of human constitutive nitric oxide synthases.,Li H, Jamal J, Plaza C, Pineda SH, Chreifi G, Jing Q, Cinelli MA, Silverman RB, Poulos TL Acta Crystallogr D Biol Crystallogr. 2014 Oct 1;70(Pt 10):2667-74. doi:, 10.1107/S1399004714017064. Epub 2014 Sep 27. PMID:25286850[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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