Language:

Structures of human constitutive nitric oxide synthases

Acta crystallographica. Section D, Biological crystallography., 2014-10, Vol.70 (10), p.2667-2674 [Peer Reviewed Journal]

International Union of Crystallography, 2014 ;International Union of Crystallography 2014 2014 ;ISSN: 1399-0047 ;ISSN: 0907-4449 ;EISSN: 1399-0047 ;DOI: 10.1107/S1399004714017064 ;PMID: 25286850

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Structures of human constitutive nitric oxide synthases
Author: Li, Huiying ; Jamal, Joumana ; Plaza, Carla ; Pineda, Stephanie Hai ; Chreifi, Georges ; Jing, Qing ; Cinelli, Maris A. ; Silverman, Richard B. ; Poulos, Thomas L.
Subjects: Aminopyridines - chemistry ; Animals ; Catalytic Domain ; Cattle ; Cloning, Molecular ; Crystallography, X-Ray ; Enzyme Inhibitors - chemistry ; Heme - chemistry ; Humans ; Models, Molecular ; nitric oxide synthase ; Nitric Oxide Synthase Type I - antagonists & inhibitors ; Nitric Oxide Synthase Type I - chemistry ; Nitric Oxide Synthase Type I - genetics ; Nitric Oxide Synthase Type I - metabolism ; Nitric Oxide Synthase Type III - antagonists & inhibitors ; Nitric Oxide Synthase Type III - chemistry ; Nitric Oxide Synthase Type III - genetics ; Nitric Oxide Synthase Type III - metabolism ; Protein Structure, Tertiary ; Pyrrolidines - chemistry ; Rats ; Research Papers
Is Part Of: Acta crystallographica. Section D, Biological crystallography., 2014-10, Vol.70 (10), p.2667-2674
Description: 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 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution.
Publisher: 5 Abbey Square, Chester, Cheshire CH1 2HU, England: International Union of Crystallography
Language: English
Identifier: ISSN: 1399-0047
ISSN: 0907-4449
EISSN: 1399-0047
DOI: 10.1107/S1399004714017064
PMID: 25286850
Source: GFMER Free Medical Journals
MEDLINE
Alma/SFX Local Collection

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Structures of human constitutive nitric oxide synthases

International Union of Crystallography, 2014 ;International Union of Crystallography 2014 2014 ;ISSN: 1399-0047 ;ISSN: 0907-4449 ;EISSN: 1399-0047 ;DOI: 10.1107/S1399004714017064 ;PMID: 25286850

Searching Remote Databases, Please Wait