Crystal structures of the nitrite and nitric oxide complexes of horse heart myoglobin

Copeland, D.M.; Soares, Alexei S.; West, Ann H.; Richter‐Addo, George B.

doi:10.1016/j.jinorgbio.2006.04.011

Cited by 104 publications

(142 citation statements)

References 100 publications

(97 reference statements)

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…We cannot conclude from our results if either binding mode is preferred, and given the differences in the heme pocket of Ngb, as compared with Mb (supplemental Fig. 5), the observations made in Mb may not extrapolate (47). Addition of a proton to the nitrite yields the nitrous acid-bound species and those can be directly formed by nitrite at low pH.…”

Section: Discussionmentioning

confidence: 71%

Human Neuroglobin Functions as a Redox-regulated Nitrite Reductase

Tiso

Tejero

Basu

et al. 2011

Journal of Biological Chemistry

251

319

View full text Add to dashboard Cite

Neuroglobin is a highly conserved hemoprotein of uncertain physiological function that evolved from a common ancestor to hemoglobin and myoglobin. It possesses a six-coordinate heme geometry with proximal and distal histidines directly bound to the heme iron, although coordination of the sixth ligand is reversible. We show that deoxygenated human neuroglobin reacts with nitrite to form nitric oxide (NO). This reaction is regulated by redox-sensitive surface thiols, cysteine 55 and 46, which regulate the fraction of the five-coordinated heme, nitrite binding, and NO formation. Replacement of the distal histidine by leucine or glutamine leads to a stable five-coordinated geometry; these neuroglobin mutants reduce nitrite to NO ϳ2000 times faster than the wild type, whereas mutation of either Cys-55 or Cys-46 to alanine stabilizes the six-coordinate structure and slows the reaction. Using lentivirus expression systems, we show that the nitrite reductase activity of neuroglobin inhibits cellular respiration via NO binding to cytochrome c oxidase and confirm that the six-to-five-coordinate status of neuroglobin regulates intracellular hypoxic NO-signaling pathways. These studies suggest that neuroglobin may function as a physiological oxidative stress sensor and a post-translationally redox-regulated nitrite reductase that generates NO under six-tofive-coordinate heme pocket control. We hypothesize that the sixcoordinate heme globin superfamily may subserve a function as primordial hypoxic and redox-regulated NO-signaling proteins.

show abstract

Section: Discussionmentioning

confidence: 71%

Human Neuroglobin Functions as a Redox-regulated Nitrite Reductase

Tiso

Tejero

Basu

et al. 2011

Journal of Biological Chemistry

251

319

View full text Add to dashboard Cite

show abstract

“…The finding that Cco functions to produce NO• from NO 2 Ϫ under hypoxic conditions places it in a group with other hemoproteins that bind O 2 under normoxic conditions and function in NO 2 Ϫ -dependent NO production under hypoxic conditions. This group includes hemoglobin and myoglobin (43)(44)(45)(46)(47). The rate of NO production by Cco increases with decreasing pH and increasing NO 2 Ϫ concentration (21), suggesting that that Cco functions in a nitrite reductase reaction (NO 2 Ϫ ϩ FeII ϩ H ϩ 3 NO ϩ FeIII ϩ OH Ϫ ) similar to that proposed for hemoglobin and myoglobin (48)(49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 86%

Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling

Castello

Woo

Ball

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

102

View full text Add to dashboard Cite

Recently, it has been reported that mitochondria possess a novel pathway for nitric oxide (NO) synthesis. This pathway is induced when cells experience hypoxia, is nitrite (NO 2 ؊ )-dependent, is independent of NO synthases, and is catalyzed by cytochrome c oxidase (Cco). It has been proposed that this mitochondrially produced NO is a component of hypoxic signaling and the induction of nuclear hypoxic genes. In this study, we examine the NO 2 ؊ -dependent NO production in yeast engineered to contain alternative isoforms, Va or Vb, of Cco subunit V. Previous studies have shown that these isoforms have differential effects on oxygen reduction by Cco, and that their genes (COX5a and COX5b, respectively) are inversely regulated by oxygen. Here, we find that the Vb isozyme has a higher turnover rate for NO production than the Va isozyme and that the Vb isozyme produces NO at much higher oxygen concentrations than the Va isozyme. We have also found that the hypoxic genes CYC7 and OLE1 are induced to higher levels in a strain carrying the Vb isozyme than in a strain carrying the Va isozyme. Together, these results demonstrate that the subunit V isoforms have differential effects on NO 2 ؊ -dependent NO production by Cco and provide further support for a role of Cco in hypoxic signaling. These findings also suggest a positive feedback mechanism in which mitochondrially produced NO induces expression of COX5b, whose protein product then functions to enhance the ability of Cco to produce NO in hypoxic/anoxic cells.hypoxia ͉ mitochondria ͉ reactive oxygen species ͉ nitrite ͉ yeast I t has been known for quite some time that the mitochondrial respiratory chain is capable of generating reactive oxygen species (ROS) that account for much of the oxidative stress experienced by cells (1-3). The levels of these ROS increase when electron flow through the respiratory chain is inhibited by respiratory inhibitors (4-6) or altered by uncoupling electron transport from oxidative phosphorylation (7,8). Several studies have shown that exposure of cells and tissues to hypoxia increases ROS levels and oxidative stress (9-11). This increase in oxidative stress during exposure to hypoxia depends on a functional mitochondrial respiratory chain (10). It is currently unclear whether this increase is the result of increased generation or decreased destruction of ROS under hypoxic conditions. In yeast cells, the increase in ROS levels and oxidative stress is transient, as determined by shifting cells from normoxia to anoxia (10). During this shift, cells experience a continuum of decreasing oxygen concentrations and a transient increase in the levels of carbonylation of both mitochondrial and cytosolic protein, an increase in 8-OH-dG levels in mtDNA, and an increase in expression of the SOD1 gene. Many of the proteins that are carbonylated during a shift from normoxia to anoxia are the same proteins that are carbonylated when cells are exposed to menadione, a redox recycling agent that produces elevated intracellular levels of superoxide (12). ...

show abstract

“…The metal-N NO bond lengths for the above M II (TPP)(NO) complexes follow the order 1.644, 1.717, and 1.837 Å for M ¼ Mn, Fe, or Co, respectively [17]. In addition, structural studies also show that the Fe-N NO bond is tilted a few degrees from perpendicular to the porphyrin plane in Fe II (TPP)(NO), and this is common for ferrous heme nitrosyls [18].…”

Section: Metal-nitrosyl Bondingmentioning

confidence: 86%

“…Notably, the complex is not very stable, and NO readily dissociates from the Cu coordination site. Table 1 summarizes some structural and IR spectral data for examples of heme and non-heme iron nitrosyls and of copper nitrosyls [17,18,[36][37][38][39][40][41][42][43][44][45][46].…”

Section: Mechanisms Of Nitric Oxide Reactions Mediated By Biologicallmentioning

confidence: 99%

“…Ford et al repulsion between the methyl groups of the respective dmp ligands that favors the tetrahedral coordination of Cu(I) over the tetragonal pyramidal structure of Cu(II). In methanol, Cu(dmp) 2 (H 2 O) 2+ reacts with NO to give Cu(dmp) 2 + and methyl nitrite (18); in water, the second product is NO 2 - [134]. In CH 2 Cl 2 , the reaction does not occur unless methanol is added.…”

Section: Reduction Of Copper(ii) Complexes By Nomentioning

confidence: 99%

See 1 more Smart Citation