Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für medizinische Forschung     Collection: Abteilung Biomolekulare Mechanismen     Display Documents



  history
ID: 124864.0, MPI für medizinische Forschung / Abteilung Biomolekulare Mechanismen
Structural Basis for the Specificity of the Nitric-oxide Synthase Inhibitors W1400 and Nω-Propyl-L-Arg for the Inducible and Neuronal Isoforms
Authors:Federov, Roman; Hartmann, Elisabeth; Ghosh, Dipak K.; Schlichting, Ilme
Language:English
Date of Publication (YYYY-MM-DD):2003-11-14
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J. Biol. Chem.
Volume:278
Issue / Number:46
Start Page:45818
End Page:45825
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:The high level of amino acid conservation and structural similarity in the immediate vicinity of the substrate binding sites of the oxygenase domains of the nitric-oxide synthase (NOS) isoforms (eNOSoxy, iNOSoxy, and nNOSoxy) make the interpretation of the structural basis of inhibitor isoform specificity a challenge and provide few clues for the design of new selective compounds. Crystal structures of iNOSoxy and nNOSoxy complexed with the inhibitors W1400 and N-propyl-L-arginine provide a rationale for their isoform specificity. It involves differences outside the immediate active site as well as a conformational flexibility in the active site that allows the adoption of distinct conformations in response to interactions with the inhibitors. This flexibility is determined by isoform-specific residues outside the active site.
Free Keywords:NOS, nitric-oxide synthase; NOSoxy, oxygenase domain of NOS; iNOS, inducible NOS; eNOS, endothelial NOS; nNOS, neuronal NOS; EPPS, N-(2-hydroxyethyl)piperazine-N'-(3-propane sulfonic acid); H4B, (6R)-5,6,7,8-tetrahydro-L-biopterin; NO, nitric oxide; SAR, structure activity relationship; ESRF, European Synchrotron Radiation Facility; DESY, Deutsches Elektronen Synchrotron
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Biomolekulare Mechanismen
Relations:-URI:http://www.pnas.org/cgi/content/full/101/16/5892
-URI:http://www.jbc.org/cgi/external_ref?access_num=10.1021/jm990111c&link_type=DOI
Identifiers:URI:http://www.jbc.org/cgi/content/abstract/278/46/458... [Abstract HTML]
URI:http://www.jbc.org/cgi/content/full/278/46/45818 [Fulltext HTML]
URI:http://www.jbc.org/cgi/reprint/278/46/45818 [Fulltext PDF]
DOI:10.1074/jbc.M306030200
LOCALID:6048 [PUMA publication management ID]
Full Text:
Sorry, no privileges
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.