Transplanting a unique allosteric effect from crocodile into human haemoglobin

  title={Transplanting a unique allosteric effect from crocodile into human haemoglobin},
  author={N. Komiyama and G. Miyazaki and J. Tame and K. Nagai},
CROCODILES are able to remain under water for more than one hour without surfacing to breathe1,2 and often kill their prey by drowning it. How do crocodiles stay under water for a long time? When they hold their breath, bicarbonate ions, the final product of respiration, accumulate and drastically reduce the oxygen affinity of haemoglobin, releasing a large fraction of haemoglobin-bound oxygen into the tissues3,4. We have now located the bicarbonate-ion-binding site at the α1β2-subunit… Expand
New insights into the allosteric effects of CO2 and bicarbonate on crocodilian hemoglobin.
Crocodilians are unique among vertebrates in that their hemoglobin (Hb) O2 binding is allosterically regulated by bicarbonate, which forms in the red blood cell upon hydration of CO2. Although knownExpand
Structure and function of crocodilian hemoglobins and allosteric regulation by chloride, ATP and CO2.
The first comparative analysis of blood properties and Hb structure and function in a phylogenetically diverse set of crocodilian species is presented, suggesting that allosteric ATP-binding has a somewhat different structural basis in crocodilian and mammalian Hbs. Expand
The Bohr effect of haemoglobin in vertebrates: an example of molecular adaptation to different physiological requirements.
A description of the general concepts at the basis of the Bohr effect as exemplified by human HbA and the analysis of the modulation mechanisms which have been observed in different animals in response to the needs induced by life in cold environments, indicating a complex organization of the information contained in the Hb molecule. Expand
Purification, Characterization, and Crystallization of Crocodylus siamensis Hemoglobin
Crude C. siamensis Hb solutions were showed high O2 affinity at P50 of 2.5 mmHg which may assure efficient utilization of the lung O2 reserve during breath holding and diving, and the purified Hb was changed to cyanmethemoglobin forms prior crystallization. Expand
Structural basis for the Root effect in haemoglobin
Surprisingly, a set of residues specific to Root effect haemoglobins recruit additional residues, conserved among most haemglobins, to produce the Root effect. Expand
Lack of conventional oxygen-linked proton and anion binding sites does not impair allosteric regulation of oxygen binding in dwarf caiman hemoglobin.
On the basis of its singular properties, P. palpebrosus Hb provides a unique opportunity for studies on structure-function coupling and the evolution of compensatory mechanisms for maintaining tissue O2 delivery in Hbs that lack conventional effector-binding residues. Expand
Crystal Structures of Deoxy- and Carbonmonoxyhemoglobin F1 from the Hagfish Eptatretus burgeri *
The results suggest that the formation of the α2β2 tetramer using the BGH core and the mechanism of quaternary structure change evolved between the branching points of hagfish and lampreys from other vertebrates. Expand
Cloning and Expression of Crocodile (Crocodylus siamensis) Hemoglobin Student: Mr. Thai Kabbua
Hemoglobin (Hb) is a major component in red blood cell of vertebrates, plays an important role in oxygen transfer from lung to tissues. Moreover, hemoglobin can be a source of bioactive peptides withExpand
Physicochemical properties and oxygen affinity of glutaraldehyde polymerized crocodile hemoglobin: the new alternative hemoglobin source for hemoglobin-based oxygen carriers
It is interesting to note that Poly-cHb may advantageously provide effective oxygen carriage and ability for pasteurization, which may benefit the search for new alternative hemoglobin sources for HBOC development. Expand
Gene therapy: a novel way to treat respiratory failure?
  • P. Kamoun
  • Biology, Medicine
  • Medical hypotheses
  • 2014
The in vitro production of Scuba hemoglobin by human hematopoietic stem cells and their reintroduction into the blood could be an interesting tool to improve tissue oxygenation in patients suffering from respiratory failure. Expand


Allosteric regulation of crocodilian haemoglobin
It is proposed that a few of the substitutions abolish or weaken the binding sites for the usual allosteric effectors and create a new pair of binding sites which are complementary to bicarbonate ions in the deoxy (T) structure, but not in the oxy (R) structure. Expand
Carbon dioxide governs the oxygen affinity of crocodile blood
It is shown that the oxygen affinity of haemoglobin from a member of the order crocodiles (Crocodylus porosus) is not affected by any of the regulating allosteric cofactors known with the exception of molecular CO2 and protons. Expand
Analysis of bicarbonate binding to crocodilian hemoglobin.
Crocodilian hemoglobin has a high intrinsic oxygen affinity but does not react with those organic phosphate esters that normally control the oxygen affinity of blood in higher vertebrates. Instead,Expand
Neither whole-blood oxygen-affinity nor ATP level was altered in response to an experimental 7-day exposure to low ambient oxygen levels, and the results do not lend themselves easily to the pan-selectionist paradigm in which all physiological traits are viewed as being adaptive. Expand
Species adaptation in a protein molecule.
  • M. Perutz
  • Biology, Medicine
  • Molecular biology and evolution
  • 1983
The results indicate that the tertiary and quaternary structures of deoxy- and oxyhemoglobin have remained almost invariant during vertebrate evolution and that most of the amino acid replacements between species are functionally neutral. Expand
Was the loss of the D helix in α globin a functionally neutral mutation?
Testing the idea that deletion of the D helix by α globin occurred shortly before tetrameric haemoglobin appeared, it might be a functionally important mutation required for a tetramer assembly or allostery is tested by engineering human haemoglobins containing β subunits without a D helIX and α subunits with a DHelix. Expand
Stereochemistry of Cooperative Effects in Haemoglobin: Haem–Haem Interaction and the Problem of Allostery
The oxygenation of haemoglobin is accompanied by structural changes in the subunits triggered by shifts of the iron atoms relative to the porphyrin and, in the β-subunits, also by the steric effectExpand
Expression of fully functional tetrameric human hemoglobin in Escherichia coli.
  • S. Hoffman, D. Looker, +4 authors G. Stetler
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1990
This system provides a simple method for expressing large quantities of recombinant hemoglobin and allows facile manipulation of the genes encoding hemoglobin to produce functionally altered forms of this protein. Expand
Physiological adjustments to prolonged diving in the American alligator, Alligator mississippiensis.
  • H. Andersen
  • Biology, Medicine
  • Acta physiologica Scandinavica
  • 1961
Results indicate that the “diving reflexes” occur in a wide variety of vertebrate divers belonging to different phylogenetic groups and enable the alligator to make the limited oxygen stores last throughout prolonged periods of submersion. Expand
Correlation between the abundance of yeast transfer RNAs and the occurrence of the respective codons in protein genes. Differences in synonymous codon choice patterns of yeast and Escherichia coli with reference to the abundance of isoaccepting transfer RNAs.
  • T. Ikemura
  • Biology, Medicine
  • Journal of molecular biology
  • 1982
Clear correlations between predictions and the actual preferences among synonymous codons were revealed, indicating that the codon choices in yeast genes are also constrained by a combination of tRNA availability and nature of its codon recognition. Expand