PDBsum entry 2r1h

Oxygen binding

PDB id: 2r1h

Contents

Protein chains

143 a.a. *

147 a.a. *

Ligands

HEM ×4

EDO ×5

Waters ×352

* Residue conservation analysis

PDB id:

2r1h

Name:

Oxygen binding

Title:

Met-trout iv hemoglobin at ph 6.3

Structure:

Hemoglobin subunit alpha-4. Chain: a, c. Synonym: hemoglobin alpha-4 chain, alpha-4- globin. Hemoglobin subunit beta-4. Chain: b, d. Synonym: hemoglobin beta-4 chain, beta-4-globin, hemoglobin beta-iv chain

Source:

Oncorhynchus mykiss. Rainbow trout. Organism_taxid: 8022. Organism_taxid: 8022

Resolution:

1.90Å R-factor: 0.172 R-free: 0.220

Authors:

R.Aranda Iv,C.E.Worley,M.P.Richards,G.N.Phillips Jr.

Key ref:

R.Aranda et al. (2008). Structural analysis of fish versus mammalian hemoglobins: Effect of the heme pocket environment on autooxidation and hemin loss. Proteins, 75, 217-230. PubMed id: 18831041 DOI: 10.1002/prot.22236

Date:

22-Aug-07 Release date: 02-Sep-08

Protein chains

P14527  (HBA4_ONCMY) -  Hemoglobin subunit alpha-4 from Oncorhynchus mykiss

Seq: 142 a.a.

Struc: 142 a.a.

Protein chains

P02141  (HBB4_ONCMY) -  Hemoglobin subunit beta-4 from Oncorhynchus mykiss

Seq: 148 a.a.

Struc: 147 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1002/prot.22236

Proteins 75:217-230 (2008)

PubMed id: 18831041

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

R.Aranda, H.Cai, C.E.Worley, E.J.Levin, R.Li, J.S.Olson, G.N.Phillips, M.P.Richards.

ABSTRACT

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 approximately 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(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 ( approximately 8 A) compared with trout IV Hb ( approximately 6 A) which in turn is significantly higher than that in bovine Hb ( approximately 4 A) 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. Proteins 2009. (c) 2008 Wiley-Liss, Inc.

Selected figure(s)

Figure 1.
Figure 1. Mechanism of iron oxidation in heme. The heme iron can be oxidized in two mechanisms: when the concentration of O[2] is high (the top method) or low (the bottom method) (based on Ref.[14]). Under high concentrations of O[2] (1), a hydronium molecule bonds with O[2] and the ligand leaves as a neutral superoxide radical. Water can then hydrogen bond with the distal His. Under low concentrations of O[2] (2), a water molecule can displace the ligand. Re-entry of O[2] can remove an electron from the heme iron in which the coordinated water facilitates the removal of the iron electron to O[2]. The ligand leaves the heme pocket as superoxide anion radical. In both scenarios the iron heme is oxidized to Fe(III).

Figure 2.
Figure 2. A: Tetrameric structure of bovine Hb at pH 5.7 (heme groups are shown in red). B: Highlighted amino acid differences in the E helix and CD turn. The structure of the trout IV subunit is shown. The amino acid residues listed in Table VI are highlighted in red and labeled. The C, D, E, and F helices and the CD turn are labeled along with the heme and proximal and distal histidine residues.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 75, 217-230) copyright 2008.

Figures were selected by an automated process.