Language:

Mechanism and regulation of ferrous heme-nitric oxide (NO) oxidation in NO synthases

The Journal of biological chemistry, 2019-05, Vol.294 (19), p.7904-7916 [Peer Reviewed Journal]

2019 © 2019 Tejero et al. ;2019 Tejero et al. ;Distributed under a Creative Commons Attribution 4.0 International License ;2019 Tejero et al. 2019 Tejero et al. ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1074/jbc.RA119.007810 ;PMID: 30926606

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:
Mechanism and regulation of ferrous heme-nitric oxide (NO) oxidation in NO synthases
Author: Tejero, Jesús ; Hunt, Andrew P. ; Santolini, Jérôme ; Lehnert, Nicolai ; Stuehr, Dennis J.
Subjects: Amino Acid Substitution ; Animals ; computational biology ; dioxygenation ; enzyme kinetics ; enzyme mechanism ; Enzymology ; Heme ; heme protein ; heme-thiolate ; Life Sciences ; Mice ; Models, Chemical ; Mutation, Missense ; nitric oxide ; Nitric Oxide - chemistry ; Nitric Oxide - genetics ; Nitric Oxide - metabolism ; Nitric Oxide Synthase Type I - chemistry ; Nitric Oxide Synthase Type I - genetics ; Nitric Oxide Synthase Type I - metabolism ; Nitric Oxide Synthase Type II - chemistry ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; nitric-oxide synthase ; Oxidation-Reduction ; Rats ; reaction mechanism ; redox reaction ; thermodynamics
Is Part Of: The Journal of biological chemistry, 2019-05, Vol.294 (19), p.7904-7916
Description: Nitric oxide (NO) synthases (NOSs) catalyze the formation of NO from l-arginine. We have shown previously that the NOS enzyme catalytic cycle involves a large number of reactions but can be characterized by a global model with three main rate-limiting steps. These are the rate of heme reduction by the flavin domain (kr), of dissociation of NO from the ferric heme-NO complex (kd), and of oxidation of the ferrous heme-NO complex (kox). The reaction of oxygen with the ferrous heme-NO species is part of a futile cycle that does not directly contribute to NO synthesis but allows a population of inactive enzyme molecules to return to the catalytic cycle, and thus, enables a steady-state NO synthesis rate. Previously, we have reported that this reaction does involve the reaction of oxygen with the NO-bound ferrous heme complex, but the mechanistic details of the reaction, that could proceed via either an inner-sphere or an outer-sphere mechanism, remained unclear. Here, we present additional experiments with neuronal NOS (nNOS) and inducible NOS (iNOS) variants (nNOS W409F and iNOS K82A and V346I) and computational methods to study how changes in heme access and electronics affect the reaction. Our results support an inner-sphere mechanism and indicate that the particular heme-thiolate environment of the NOS enzymes can stabilize an N-bound FeIII-N(O)OO− intermediate species and thereby catalyze this reaction, which otherwise is not observed or favorable in proteins like globins that contain a histidine-coordinated heme.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0021-9258
EISSN: 1083-351X
DOI: 10.1074/jbc.RA119.007810
PMID: 30926606
Source: MEDLINE
PubMed Central
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

Mechanism and regulation of ferrous heme-nitric oxide (NO) oxidation in NO synthases

2019 © 2019 Tejero et al. ;2019 Tejero et al. ;Distributed under a Creative Commons Attribution 4.0 International License ;2019 Tejero et al. 2019 Tejero et al. ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1074/jbc.RA119.007810 ;PMID: 30926606

Searching Remote Databases, Please Wait