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Current ProjectsBlood SubstitutesMechanisms of Acute Kidney InjuryMetal Isotope and Magnetic Field Effects on Protein KinasesStructure and Function of Non-Symbiotic Plant Haemoglobins Biophysics and Physiological Function of Human Cytoglobin

Pentacoordinate Globins:A: Sperm Whale MyoglobinB: Human Haemoglobin chainC: Yellow Lupin LeghemoglobinHexacoordinate GlobinsD: Human NeuroglobinE: Human CytoglobinF: Asian Rice Non-Symbiotic HaemoglobinHaemoglobin Superfamily: Reeder, B.J. Antioxid. Redox. Sign. (2010) 13(7) 1088-1123Interaction of Cytoglobin with lipids changes structure of the protein

Various Lipids and Lipid-like molecules cause a change from 6 to 5 coordinate iron ligation state

Reeder, B.J., Svistunenko, D.A. & Wilson M.T. Lipid binding to cytoglobin leads to a change in haem co-ordination: a role for cytoglobin in lipid signalling of oxidative stress Biochem. J. (2011) 434, 483492Stopped FlowLaser FlashEPR

What is the Mechanism of the Cytoglobin Cell Protection?

Haemoglobins in PlantsNon-symbiotic plant haemoglobins (nsHbs)

Discovered from genomic sequencing in mid-90s.

Three classes of nsHbs:

Class 1 nsHb: related to leghaemoglobin, but with hexacoordinate haem iron. Expressed in both roots and rosette leaves. Forms stable O2 complex with very high O2 affinity (Kd~2-10nM). Known structure for rice and corn (but not Arabidopsis-until now).

Class 2 nsHb: Hexacoordinate globin ~60% sequence homology to class 1 proteins. Lower O2 affinity (Kd~150nM). Induced in rosette leaves at low temperatures. Very high auto-oxidation rate. No structures known.

Class 3 nsHb: Sequence suggests a truncated 2/2 -helical structure like bacterial truncated Hb. Very little information available. Very few papers. No structures known.

Too high kd for o2 carrying function5Crystal Structure of A. thaliana Hb3

Comparison of AHb3 structure (red) with haemoglobin from Bacillus subtilis (blue)

AHb3 Structure to1.77 Resolution

1.776

Magnesium Isotope and Magnetic Field Effects on Creatine Kinase Activity

Earthquakes and Acute Kidney InjuryThe Spitak Earthquake (Armenia 1988) 25,000+ casualties600-1000 survivors developed Rhabdomyolysis of which 225-385 developed Acute Kidney Injury (Acute Renal Failure).

Many fatalities due to inadequate renal treatment facilities (dialysis machines)

In England up to 750,000 are effected by Acute Kidney Injury at a cost of ~600 million to NHS (5-25% due to rhabdomyolysis).

Reeder, B.J., Grey, M., Silaghi-Dumitrescu, R., Svistunenko, D.A., Blow, L., Cooper, C.E. & Wilson, M.T Tyrosine residues as redox cofactors in human hemoglobin: Implications for engineering non toxic blood substitutes J. Biol. Chem (2008) 283(45), 30780-30787Blood Substitutes

Can we Engineer a less toxic blood substitute?Current/Developing Collaborations:Cytoglobin: Dr Dima Svistunenko (Essex)Prof Geoff Moore (UEA)Dr Marten Vos (Ecole, France)Dr Philippe Laissue (Essex)Dr Metodi Metodiev (Essex)

Plant Haemoglobin:Dr Mike Hough (Essex)Prof Leif Bulow (Lund, Sweden)Prof Phil Mullineaux (Essex)Dr Dima Svistunenko (Essex)

EMF:Prof Mike Wilson (Essex)Dr Gary Silkstone (Essex)Prof Robert Hider (Kings C., London)

Acute Kidney injury: Professor Kevin Moore, UCLProf Chris Cooper (Essex)Prof L. Jackson Roberts II (Vanderbilt, USA)Dr Sinan Battah (Essex/UCL)

Blood Substitutes: Prof Chris Cooper (Essex)Dr Gary Silkstone (Essex)Prof Andrea Mozzarelli (Parma, Italy)Prof Leif Bulow (Lund, Sweden)