Structural analysis of fish versus mammalian hemoglobins: Effect of the heme pocket environment on autooxidation and hemin loss

Journal Article · Thu Jan 07 00:00:00 EST 2010 · Proteins

DOI:https://doi.org/10.1002/prot.22236· OSTI ID:1005664

Aranda, IV, Roman; Cai, He; Worley, Chad E; Levin, Elena J; Li, Rong; Olson, John S; Richards, Mark P

The underlying stereochemical mechanisms for the dramatic differences in autooxidation and hemin loss rates of fish versus mammalian hemoglobins (Hb) have been examined by determining the crystal structures of perch, trout IV, and bovine Hb at high and low pH. The fish Hbs autooxidize and release hemin {approx}50- to 100-fold more rapidly than bovine Hb. Five specific amino acid replacements in the CD corner and along the E helix appear to cause the increased susceptibility of fish Hbs to oxidative degradation compared with mammalian Hbs. Ile is present at the E11 helical position in most fish Hb chains whereas a smaller Val residue is present in all mammalian {alpha} and {beta} chains. The larger IleE11 side chain sterically hinders bound O{sub 2} and facilitates dissociation of the neutral superoxide radical, enhancing autooxidation. Lys(E10) is found in most mammalian Hb and forms favorable electrostatic and hydrogen bonding interactions with the heme-7-propionate. In contrast, Thr(E10) is present in most fish Hbs and is too short to stabilize bound heme, and causes increased rates of hemin dissociation. Especially high rates of hemin loss in perch Hb are also due to a lack of electrostatic interaction between His(CE3) and the heme-6 propionate in {alpha} subunits whereas this interaction does occur in trout IV and bovine Hb. There is also a larger gap for solvent entry into the heme crevice near {beta} CD3 in the perch Hb ({approx}8 {angstrom}) compared with trout IV Hb ({approx}6 {angstrom}) which in turn is significantly higher than that in bovine Hb ({approx}4 {angstrom}) at low pH. The amino acids at CD4 and E14 differ between bovine and the fish Hbs and have the potential to modulate oxidative degradation by altering the orientation of the distal histidine and the stability of the E-helix. Generally rapid rates of lipid oxidation in fish muscle can be partly attributed to the fact that fish Hbs are highly susceptible to oxidative degradation.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States)
• Sponsoring Organization: USDOE
• OSTI ID: 1005664
• Journal Information: Proteins, Vol. 75, Issue (1) ; 04, 2009; ISSN 0887-3585
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

08 HYDROGEN
36 MATERIALS SCIENCE
AFFINITY
AMINO ACIDS
BONDING
CATTLE
CHAINS
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
DISSOCIATION
ELECTROSTATICS
HEME
HISTIDINE
HYDROGEN
INTERACTIONS
LIPIDS
MUSCLES
MYOGLOBIN
ORIENTATION
OXIDATION
POTENTIALS
PROTEINS
REDOX REACTIONS
RESIDUES
SOLVENTS
STABILITY
SUPEROXIDE RADICALS
TROUT