PDBsum entry 1i3e

Oxygen storage/transport

PDB id: 1i3e

Contents

Protein chains

146 a.a. *

Ligands

AZI-HEM ×2

Waters ×242

* Residue conservation analysis

PDB id:

1i3e

Name:

Oxygen storage/transport

Title:

Human azido-met hemoglobin bart's (gamma4)

Structure:

Hemoglobin gamma chains. Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hbg1. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.86Å R-factor: 0.184 R-free: 0.220

Authors:

R.D.Kidd,H.M.Baker,A.J.Mathews,T.Brittain,E.N.Baker

Key ref:

R.D.Kidd et al. (2001). Oligomerization and ligand binding in a homotetrameric hemoglobin: two high-resolution crystal structures of hemoglobin Bart's (gamma(4)), a marker for alpha-thalassemia. Protein Sci, 10, 1739-1749. PubMed id: 11514664

Date:

15-Feb-01 Release date: 12-Sep-01

Protein chains

P69891  (HBG1_HUMAN) -  Hemoglobin subunit gamma-1 from Homo sapiens

Seq: 147 a.a.

Struc: 146 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Protein Sci 10:1739-1749 (2001)

PubMed id: 11514664

Oligomerization and ligand binding in a homotetrameric hemoglobin: two high-resolution crystal structures of hemoglobin Bart's (gamma(4)), a marker for alpha-thalassemia.

R.D.Kidd, H.M.Baker, A.J.Mathews, T.Brittain, E.N.Baker.

ABSTRACT

Hemoglobin (Hb) Bart's is present in the red blood cells of millions of people worldwide who suffer from alpha-thalassemia. alpha-Thalassemia is a disease in which there is a deletion of one or more of the four alpha-chain genes, and excess gamma and beta chains spontaneously form homotetramers. The gamma(4) homotetrameric protein known as Hb Bart's is a stable species that exhibits neither a Bohr effect nor heme-heme cooperativity. Although Hb Bart's has a higher O(2) affinity than either adult (alpha(2)beta(2)) or fetal (alpha(2)gamma(2)) Hbs, it has a lower affinity for O(2) than HbH (beta(4)). To better understand the association and ligand binding properties of the gamma(4) tetramer, we have solved the structure of Hb Bart's in two different oxidation and ligation states. The crystal structure of ferrous carbonmonoxy (CO) Hb Bart's was determined by molecular replacement and refined at 1.7 A resolution (R = 21.1%, R(free) = 24.4%), and that of ferric azide (N(3)(-)) Hb Bart's was similarly determined at 1.86 A resolution (R = 18.4%, R(free) = 22.0%). In the carbonmonoxy-Hb structure, the CO ligand is bound at an angle of 140 degrees, and with an unusually long Fe-C bond of 2.25 A. This geometry is attributed to repulsion from the distal His63 at the low pH of crystallization (4.5). In contrast, azide is bound to the oxidized heme iron in the methemoglobin crystals at an angle of 112 degrees, in a perfect orientation to accept a hydrogen bond from His63. Compared to the three known quaternary structures of human Hb (T, R, and R2), both structures most closely resemble the R state. Comparisons with the structures of adult Hb and HbH explain the association and dissociation behaviour of Hb homotetramers relative to the heterotetrameric Hbs.