1niw
From Proteopedia
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|PDB= 1niw |SIZE=350|CAPTION= <scene name='initialview01'>1niw</scene>, resolution 2.05Å | |PDB= 1niw |SIZE=350|CAPTION= <scene name='initialview01'>1niw</scene>, resolution 2.05Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1niw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1niw OCA], [http://www.ebi.ac.uk/pdbsum/1niw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1niw RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The enzyme nitric oxide synthase (NOS) is exquisitely regulated in vivo by the Ca(2+) sensor protein calmodulin (CaM) to control production of NO, a key signaling molecule and cytotoxin. The differential activation of NOS isozymes by CaM has remained enigmatic, despite extensive research. Here, the crystallographic structure of Ca(2+)-loaded CaM bound to a 20 residue peptide comprising the endothelial NOS (eNOS) CaM-binding region establishes their individual conformations and intermolecular interactions, and suggests the basis for isozyme-specific differences. The alpha-helical eNOS peptide binds in an antiparallel orientation to CaM through extensive hydrophobic interactions. Unique NOS interactions occur with: (i). the CaM flexible central linker, explaining its importance in NOS activation; and (ii). the CaM C-terminus, explaining the NOS-specific requirement for a bulky, hydrophobic residue at position 144. This binding mode expands mechanisms for CaM-mediated activation, explains eNOS deactivation by Thr495 phosphorylation, and implicates specific hydrophobic residues in the Ca(2+) independence of inducible NOS. | The enzyme nitric oxide synthase (NOS) is exquisitely regulated in vivo by the Ca(2+) sensor protein calmodulin (CaM) to control production of NO, a key signaling molecule and cytotoxin. The differential activation of NOS isozymes by CaM has remained enigmatic, despite extensive research. Here, the crystallographic structure of Ca(2+)-loaded CaM bound to a 20 residue peptide comprising the endothelial NOS (eNOS) CaM-binding region establishes their individual conformations and intermolecular interactions, and suggests the basis for isozyme-specific differences. The alpha-helical eNOS peptide binds in an antiparallel orientation to CaM through extensive hydrophobic interactions. Unique NOS interactions occur with: (i). the CaM flexible central linker, explaining its importance in NOS activation; and (ii). the CaM C-terminus, explaining the NOS-specific requirement for a bulky, hydrophobic residue at position 144. This binding mode expands mechanisms for CaM-mediated activation, explains eNOS deactivation by Thr495 phosphorylation, and implicates specific hydrophobic residues in the Ca(2+) independence of inducible NOS. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Coronary spasms, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Hypertension, pregnancy-induced OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Hypertension, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Ischemic stroke, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Placental abruption OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Getzoff, E D.]] | [[Category: Getzoff, E D.]] | ||
[[Category: Tainer, J A.]] | [[Category: Tainer, J A.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: EDO]] | ||
| - | [[Category: SO4]] | ||
[[Category: calcium-binding protein]] | [[Category: calcium-binding protein]] | ||
[[Category: nitric oxide]] | [[Category: nitric oxide]] | ||
[[Category: no]] | [[Category: no]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:31:02 2008'' |
Revision as of 19:31, 30 March 2008
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| , resolution 2.05Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of endothelial nitric oxide synthase peptide bound to calmodulin
Overview
The enzyme nitric oxide synthase (NOS) is exquisitely regulated in vivo by the Ca(2+) sensor protein calmodulin (CaM) to control production of NO, a key signaling molecule and cytotoxin. The differential activation of NOS isozymes by CaM has remained enigmatic, despite extensive research. Here, the crystallographic structure of Ca(2+)-loaded CaM bound to a 20 residue peptide comprising the endothelial NOS (eNOS) CaM-binding region establishes their individual conformations and intermolecular interactions, and suggests the basis for isozyme-specific differences. The alpha-helical eNOS peptide binds in an antiparallel orientation to CaM through extensive hydrophobic interactions. Unique NOS interactions occur with: (i). the CaM flexible central linker, explaining its importance in NOS activation; and (ii). the CaM C-terminus, explaining the NOS-specific requirement for a bulky, hydrophobic residue at position 144. This binding mode expands mechanisms for CaM-mediated activation, explains eNOS deactivation by Thr495 phosphorylation, and implicates specific hydrophobic residues in the Ca(2+) independence of inducible NOS.
About this Structure
1NIW is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural basis for endothelial nitric oxide synthase binding to calmodulin., Aoyagi M, Arvai AS, Tainer JA, Getzoff ED, EMBO J. 2003 Feb 17;22(4):766-75. PMID:12574113
Page seeded by OCA on Sun Mar 30 22:31:02 2008
