5E6E

Crystal Structure of Carbonmonoxy Sickle Hemoglobin in R-State Conformation

Summary for 5E6E

• Entry DOI: 10.2210/pdb5e6e/pdb
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, CARBON MONOXIDE, ... (7 entities in total)
• Functional Keywords: sickle cell, hemoglobin, r-state, allosteric, oxygen transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 32578.81

Authors

Safo, M.K.,Ahmed, M.H. (deposition date: 2015-10-09, release date: 2015-10-28, Last modification date: 2023-09-27)

Primary citation

Ghatge, M.S.,Ahmed, M.H.,Omar, A.S.,Pagare, P.P.,Rosef, S.,Kellogg, G.E.,Abdulmalik, O.,Safo, M.K.
Crystal structure of carbonmonoxy sickle hemoglobin in R-state conformation.
J.Struct.Biol., 194:446-450, 2016

PubMed 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.

PubMed: 27085422
DOI: 10.1016/j.jsb.2016.04.003

Experimental method

X-RAY DIFFRACTION (1.76 Å)