PDBsum entry 2hhd

Oxygen transport

PDB id: 2hhd

Contents

Protein chains

141 a.a. *

146 a.a. *

Ligands

HEM ×4

SO4 ×2

Waters ×474

* Residue conservation analysis

PDB id:

2hhd

Name:

Oxygen transport

Title:

Oxygen affinity modulation by the n-termini of the beta-chains in human and bovine hemoglobin

Structure:

Hemoglobin (deoxy) (alpha chain). Chain: a, c. Engineered: yes. Hemoglobin (deoxy) (beta chain). Chain: b, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: blood. Tissue: blood. Tissue: blood

Biol. unit:

Tetramer (from PQS)

Resolution:

2.20Å R-factor: 0.137

Authors:

G.L.Gilliland,I.Pechik,C.Fronticelli,X.Ji

Key ref:

I.Pechik et al. (1996). Crystallographic, molecular modeling, and biophysical characterization of the valine beta 67 (E11)-->threonine variant of hemoglobin. Biochemistry, 35, 1935-1945. PubMed id: 8639677 DOI: 10.1021/bi9519967

Date:

29-Sep-94 Release date: 26-Jan-95

Protein chains

P69905  (HBA_HUMAN) -  Hemoglobin subunit alpha from Homo sapiens

Seq: 142 a.a.

Struc: 141 a.a.

Protein chains

P68871  (HBB_HUMAN) -  Hemoglobin subunit beta from Homo sapiens

Seq: 147 a.a.

Struc: 146 a.a.

DOI no: 10.1021/bi9519967

Biochemistry 35:1935-1945 (1996)

PubMed id: 8639677

Crystallographic, molecular modeling, and biophysical characterization of the valine beta 67 (E11)-->threonine variant of hemoglobin.

I.Pechik, X.Ji, K.Fidelis, M.Karavitis, J.Moult, W.S.Brinigar, C.Fronticelli, G.L.Gilliland.

ABSTRACT

The crystal structure of the mutant deoxyhemoglobin in which the beta-globin Val67(E11) has been replaced with threonine [Fronticelli et al. (1993) Biochemistry 32, 1235-1242] has been determined at 2.2 A resolution. Prior to the crystal structure determination, molecular modeling indicated that the Thr67(E11) side chain hydroxyl group in the distal beta-heme pocket forms a hydrogen bond with the backbone carbonyl of His63(E7) and is within hydrogen-bonding distance of the N delta of His63(E7). The mutant crystal structure indicates only small changes in conformation in the vicinity of the E11 mutation confirming the molecular modeling predictions. Comparison of the structures of the mutant beta-subunits and recombinant porcine myoglobin with the identical mutation [Cameron et al. (1993) Biochemistry 32, 13061-13070] indicates similar conformations of residues in the distal heme pocket, but there is no water molecule associated with either of the threonines of the beta-subunits. The introduction of threonine into the distal heme pocket, despite having only small perturbations in the local structure, has a marked affect on the interaction with ligands. In the oxy derivative there is a 2-fold decrease in O2 affinity [Fronticelli et al. (1993) Biochemistry 32, 1235-1242], and the rate of autoxidation is increased by 2 orders of magnitude. In the CO derivative the IR spectrum shows modifications with respect to that of normal human hemoglobin, suggesting the presence of multiple CO conformers. In the nitrosyl derivative an interaction with the O gamma atom of Thr67(E11) is probably responsible for the 10-fold increase in the rate of NO release from the beta-subunits. In the aquomet derivative there is a 6-fold decrease in the rate of hemin dissociation suggesting an interaction of the Fe-coordinated water with the O gamma of Thr67(E11).