PDBsum entry 5e6e

Oxygen transport

PDB id: 5e6e

Contents

Protein chains

141 a.a.

146 a.a.

Ligands

CMO-HEM ×2

MBN ×2

PO4

Waters ×441

PDB id:

5e6e

Name:

Oxygen transport

Title:

Crystal structure of carbonmonoxy sickle hemoglobin in r-state conformation

Structure:

Hemoglobin subunit alpha. Chain: a. Synonym: alpha-globin, hemoglobin alpha chain. Engineered: yes. Hemoglobin subunit beta. Chain: b. Synonym: beta-globin, hemoglobin beta chain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hba1, hba2. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: hbb. Expression_system_taxid: 9606

Resolution:

1.76Å R-factor: 0.193 R-free: 0.243

Authors:

M.K.Safo,M.H.Ahmed

Key ref:

M.S.Ghatge et al. (2016). Crystal structure of carbonmonoxy sickle hemoglobin in R-state conformation. J Struct Biol, 194, 446-450. PubMed id: 27085422 DOI: 10.1016/j.jsb.2016.04.003

Date:

09-Oct-15 Release date: 28-Oct-15

Protein chain

P69905  (HBA_HUMAN) -  Hemoglobin subunit alpha from Homo sapiens

Seq: 142 a.a.

Struc: 141 a.a.

Protein chain

P68871  (HBB_HUMAN) -  Hemoglobin subunit beta from Homo sapiens

Seq: 147 a.a.

Struc: 146 a.a.*

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

DOI no: 10.1016/j.jsb.2016.04.003

J Struct Biol 194:446-450 (2016)

PubMed id: 27085422

Crystal structure of carbonmonoxy sickle hemoglobin in R-state conformation.

M.S.Ghatge, M.H.Ahmed, A.S.Omar, P.P.Pagare, S.Rosef, G.E.Kellogg, O.Abdulmalik, M.K.Safo.

ABSTRACT

The fundamental pathophysiology of sickle cell disease is predicated by the polymerization of deoxygenated (T-state) sickle hemoglobin (Hb S) into fibers that distort red blood cells into the characteristic sickle shape. The crystal structure of deoxygenated Hb S (DeoxyHb S) and other studies suggest that the polymer is initiated by a primary interaction between the mutation βVal6 from one Hb S molecule, and a hydrophobic acceptor pocket formed by the residues βAla70, βPhe85 and βLeu88 of an adjacent located Hb S molecule. On the contrary, oxygenated or liganded Hb S does not polymerize or incorporate in the polymer. In this paper we present the crystal structure of carbonmonoxy-ligated sickle Hb (COHb S) in the quaternary classical R-state at 1.76Å. The overall structure and the pathological donor and acceptor environments of COHb S are similar to those of the isomorphous CO-ligated R-state normal Hb (COHb A), but differ significantly from DeoxyHb S as expected. More importantly, the packing of COHb S molecules does not show the typical pathological interaction between βVal6 and the βAla70, βPhe85 and βLeu88 hydrophobic acceptor pocket observed in DeoxyHb S crystal. The structural analysis of COHb S, COHb A and DeoxyHb S provides atomic level insight into why liganded hemoglobin does not form a polymer.