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On the basis of sequence and three-dimensional structure comparison between Anabaena PCC7119 ferredoxin-NADP(+) reductase (FNR) and other reductases from its structurally related family that bind either NADP(+)/H or NAD(+)/H, a set of amino acid residues that might determine the FNR coenzyme specificity can be assigned. These residues include Thr-155,(More)
The low barometric pressure at high altitude causes lower arterial oxygen content among Tibetan highlanders, who maintain normal levels of oxygen use as indicated by basal and maximal oxygen consumption levels that are consistent with sea level predictions. This study tested the hypothesis that Tibetans resident at 4,200 m offset physiological hypoxia and(More)
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(More)
Nitric-oxide synthases (NOS) are catalytically self-sufficient flavo-heme enzymes that generate NO from arginine (Arg) and display a novel utilization of their tetrahydrobiopterin (H(4)B) cofactor. During Arg hydroxylation, H(4)B acts as a one-electron donor and is then presumed to redox cycle (i.e. be reduced back to H(4)B) within NOS before further(More)
The catalytic mechanism proposed for ferredoxin-NADP(+) reductase (FNR) is initiated by reduction of its flavin adenine dinucleotide (FAD) cofactor by the obligatory one-electron carriers ferredoxin (Fd) or flavodoxin (Fld) in the presence of oxidized nicotinamide adenine dinucleotide phosphate (NADP(+)). The C-terminal tyrosine of FNR, which stacks onto(More)
AIMS Recent studies suggest that the molybdenum enzymes xanthine oxidase, aldehyde oxidase, and mARC exhibit nitrite reductase activity at low oxygen pressures. However, inhibition studies of xanthine oxidase in humans have failed to block nitrite-dependent changes in blood flow, leading to continued exploration for other candidate nitrite reductases.(More)
The mechanism of hydride transfer between Anabaena FNR and NADP+/H was analysed using for the first time stopped-flow photodiode array detection and global analysis deconvolution. The results indicated that the initial spectral changes, occurring within the instrumental dead time upon reaction of FNR with NADP+/H, included not only the initial interaction(More)
BACKGROUND Intravascular red cell hemolysis impairs nitric oxide (NO)-redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we(More)
AIMS Hemoglobin-based oxygen carriers (HBOC) provide a potential alternative to red blood cell (RBC) transfusion. Their clinical application has been limited by adverse effects, in large part thought to be mediated by the intravascular scavenging of the vasodilator nitric oxide (NO) by cell-free plasma oxy-hemoglobin. Free hemoglobin may also cause(More)
Ferredoxin-NADP+ reductase (FNR) catalyzes the reduction of NADP+ to NADPH in an overall reversible reaction, showing some differences in the mechanisms between cyanobacterial and higher plant FNRs. During hydride transfer it is proposed that the FNR C-terminal Tyr is displaced by the nicotinamide. Thus, this C-terminal Tyr might be involved not only in(More)