Role of Distal Arginine in Early Sensing Intermediates in the Heme Domain of the Oxygen Sensor FixL†

Biochemistry ◽  
2006 ◽  
Vol 45 (19) ◽  
pp. 6018-6026 ◽  
Author(s):  
Audrius Jasaitis ◽  
Klara Hola ◽  
Latifa Bouzhir-Sima ◽  
Jean-Christophe Lambry ◽  
Veronique Balland ◽  
...  
Keyword(s):  
Oxygen Sensor ◽  
Heme Domain

Role of Phe113 at the distal side of the heme domain of an oxygen-sensor (Ec DOS) in the characterization of the heme environment

2009 ◽  
Vol 103 (7) ◽  
pp. 989-996 ◽  
Author(s):  
Shinya Ito ◽  
Yasuyuki Araki ◽  
Atsunari Tanaka ◽  
Jotaro Igarashi ◽  
Takehiko Wada ◽  
...  
Keyword(s):  
Oxygen Sensor ◽  
Distal Side ◽  
Heme Domain

Design and synthesis of novel porphyrinated polyimide nanofibers as dissolved oxygen sensor: The role of electro-activity and orientation

2019 ◽  
Vol 161 ◽  
pp. 79-88 ◽  
Author(s):  
Huanyu Lei ◽  
Jiaming Lu ◽  
Guoqing Dong ◽  
Guofeng Tian ◽  
Shengli Qi ◽  
...  
Keyword(s):  
Dissolved Oxygen ◽  
Oxygen Sensor ◽  
Design And Synthesis

Cloning, purification, crystallization and preliminary X-ray analysis of DOS heme domain, a new heme oxygen sensor inEscherichia coli

2002 ◽  
Vol 58 (9) ◽  
pp. 1504-1506 ◽  
Author(s):  
HaJeung Park ◽  
Christine Suquet ◽  
Marina I. Savenkova ◽  
James D. Satterlee ◽  
ChulHee Kang
Keyword(s):  
Oxygen Sensor ◽  
Inescherichia Coli ◽  
X Ray ◽  
Heme Domain

Ligand Binding Dynamics to the Heme Domain of the Oxygen Sensor Dos fromEscherichia coli

Biochemistry ◽  
2003 ◽  
Vol 42 (21) ◽  
pp. 6527-6535 ◽  
Author(s):  
Ursula Liebl ◽  
Latifa Bouzhir-Sima ◽  
Laurent Kiger ◽  
Michael C. Marden ◽  
Jean-Christophe Lambry ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Oxygen Sensor ◽  
Fromescherichia Coli ◽  
Heme Domain

scholarly journals A New Class of Repression Modules Is Critical for Heme Regulation of the Yeast Transcriptional Activator Hap1

1999 ◽  
Vol 19 (6) ◽  
pp. 4324-4333 ◽  
Author(s):  
Angela Hach ◽  
Thomas Hon ◽  
Li Zhang
Keyword(s):  
Biochemical Analysis ◽  
Activator Protein 1 ◽  
Heme Binding ◽  
Systematic Analysis ◽  
High Molecular Weight Complex ◽  
Cellular Processes ◽  
New Class ◽  
Heme Domain ◽  
Heme Regulation

ABSTRACTHeme plays key regulatory roles in numerous molecular and cellular processes for systems that sense or use oxygen. In the yeastSaccharomyces cerevisiae, oxygen sensing and heme signaling are mediated by heme activator protein 1 (Hap1). Hap1 contains seven heme-responsive motifs (HRMs): six are clustered in the heme domain, and a seventh is near the activation domain. To determine the functional role of HRMs and to define which parts of Hap1 mediate heme regulation, we carried out a systematic analysis of Hap1 mutants with various regions deleted or mutated. Strikingly, the data show that HRM1 to -6, located in the previously designated Hap1 heme domain, have little impact on heme regulation. All seven HRMs are dispensable for Hap1 repression in the absence of heme, but HRM7 is required for Hap1 activation by heme. More importantly, we show that a novel class of repression modules—RPM1, encompassing residues 245 to 278; RPM2, encompassing residues 1061 to 1185; and RPM3, encompassing residues 203 to 244—is critical for Hap1 repression in the absence of heme. Biochemical analysis indicates that RPMs mediate Hap1 repression, at least partly, by the formation of a previously identified higher-order complex termed the high-molecular-weight complex (HMC), while HRMs mediate heme activation by permitting heme binding and the disassembly of the HMC. These findings provide significant new insights into the molecular interactions critical for Hap1 repression in the absence of heme and Hap1 activation by heme.

Time-Resolved Crystallographic Studies of the Heme Domain of the Oxygen Sensor FixL:  Structural Dynamics of Ligand Rebinding and Their Relation to Signal Transduction†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (16) ◽  
pp. 4706-4715 ◽  
Author(s):  
Jason Key ◽  
Vukica Šrajer ◽  
Reinhard Pahl ◽  
Keith Moffat
Keyword(s):  
Signal Transduction ◽  
Structural Dynamics ◽  
Oxygen Sensor ◽  
Time Resolved ◽  
Heme Domain ◽  
Ligand Rebinding

scholarly journals Role of Arginine 220 in the Oxygen Sensor FixL fromBradyrhizobium japonicum

2005 ◽  
Vol 280 (15) ◽  
pp. 15279-15288 ◽  
Author(s):  
Véronique Balland ◽  
Latifa Bouzhir-Sima ◽  
Laurent Kiger ◽  
Michael C. Marden ◽  
Marten H. Vos ◽  
...  
Keyword(s):  
Oxygen Sensor

ID: 113: THE ENDOTHELIAL PHD2/HIF-2 AXIS REGULATES PULMONARY ARTERY PRESSURE IN MICE

2016 ◽  
Vol 64 (4) ◽  
pp. 961.2-962
Author(s):  
PP Kapitsinou ◽  
G Rajendran ◽  
L Astleford ◽  
MP Schonfeld ◽  
M Michael ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Oxygen Sensor ◽  
Acute Hypoxia ◽  
Systolic Pressure ◽  
Clinical Problem ◽  
Ventricular Systolic Pressure

BackgroundPulmonary hypertension (PH), a common clinical problem characterized by increased pulmonary artery (PA) pressure, is frequently triggered by hypoxia. Key mediators of cellular hypoxia responses are hypoxia-inducible factors (HIF)-1 and -2, the activity of which is regulated by prolyl-4-hydroxylase domain (PHD) proteins, with PHD2 being the main oxygen sensor that controls HIF activity under normoxia. Although both transcription factors are expressed in the lung, little is known about their cell type-specific roles in the pathogenesis of PH.Methods and ResultsHere we used a genetic approach to investigate the role of endothelial PHD2/HIF axis in the regulation of PA pressure. Endothelial cell specific HIF activation was achieved by crossing Vecadherin (Cdh5)-Cre transgenics to Phd2 floxed mice (ePhd2), while the contribution of each HIF isoform was assessed by generating double mutants lacking Phd2 and Hif-2 (ePhd2Hif2) or Phd2 and Hif-1 (Phd2Hif1). Right ventricular systolic pressure (RVSP) was measured via insertion of a 1.4F Mikro-tip catheter transducer into a surgically exposed right internal jugular vein. ePhd2 mice showed activation of HIF-signaling as shown by immunoblot analysis of lung tissue for HIF-1 and HIF-2. These mice developed spontaneous PH (RVSP, ePhd2: 54.3±6.9 vs Cre-: 24.8±2.2 mm Hg, P=0.005), which was associated with right ventricular hypertrophy (RVH) (Fulton Index, ePhd2: 0.52 vs Cre-: 0.28, P=0.0004) and early mortality. While morphologic analysis of ePhd2 lungs did not demonstrate plexiform or lumen-obliterating lesions, enhanced muscularization of peripheral PAs was detected in mutants compared to controls, as indicated by an increase in the number of arteries with diameters <100 µm that stained positive for αSMA (22.1±1.6 vs. 7.6±1.5 muscularized vessels/10 hpf, P<0.0001). The PH phenotype was maintained in ePhd2Hif1 mutants but was reversed in ePhd2Hif2 mutants. To assess the contribution of endothelial HIF-2 in hypoxia induced PH, endothelial Hif2 single mutants or Cre-littermates were exposed to normobaric hypoxia (10% O2) for 4 weeks. In contrast to controls, eHif2 mutants were protected from development of PH and RVH. Bone marrow transplantation studies showed no contribution from hematopoietic HIF-2 in hypoxia induced PH. Because hypoxia regulates endothelin 1 (EDN1), a potent vasoconstrictor but also apelin (APLN), a vasodilatory peptide acting through binding to the apelin G-protein-coupled receptor (APLNR), we assessed the role of endothelial HIF-2 axis in the regulation of these molecules. Endothelial deletion of Phd2 resulted in 6.4-fold induction of pulmonary Edn1 mRNA (P=0.029), but not Apln mRNA. In contrast, Aplnr was downregulated by 2.5-fold in ePhd2 mutants (P=0.037). A similar pattern of expression was detected in ePhd2Hif1 mice, whereas simultaneous deletion of Hif2a and Phd2 reversed these changes. To investigate the differences between acute and chronic hypoxia, we examined the effects of acute HIF activation on Edn1 and Apln/Aplnr gene expression in vivo. To model acute hypoxia, we subjected WT mice to 8% O2 for 48 hrs and maintained controls in room air. Acute hypoxia resulted in a 4.3-fold and 1.6-fold up-regulation of Edn1 and Apln transcripts respectively (P=0.0011 for Edn1, P=0.08 for Apln) while Aplnr was reduced by 4.3-fold (P=0.0005). We observed similar gene expression changes in mice treated with a prolyl-4-hydroxylase inhibitor (PHI) that results in global HIF activation.ConclusionsOur studies identify endothelial HIF-2 as a key transcription factor in the pathogenesis of PH and suggest that HIF-2 regulates PA pressure by modulating the expression of vasoactive molecules. Our findings identify the PHD2/HIF2 axis as a potential target for PH therapies.

P87 Role of hydrogen sulfide as an oxygen sensor in human airways

Nitric Oxide ◽  
2014 ◽  
Vol 39 ◽  
pp. S42
Author(s):  
Rob Bennett ◽  
Mubarak A. Chaudhry ◽  
Michael E. Cowen ◽  
Mahmoud Loubani ◽  
Alyn H. Morice
Keyword(s):  
Hydrogen Sulfide ◽  
Oxygen Sensor ◽  
Human Airways
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