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PDBsum entry 5e6e
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Oxygen transport
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PDB id
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5e6e
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References listed in PDB file
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Key reference
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Title
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Crystal structure of carbonmonoxy sickle hemoglobin in r-State conformation.
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Authors
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M.S.Ghatge,
M.H.Ahmed,
A.S.Omar,
P.P.Pagare,
S.Rosef,
G.E.Kellogg,
O.Abdulmalik,
M.K.Safo.
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Ref.
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J Struct Biol, 2016,
194,
446-450.
[DOI no: ]
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PubMed id
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Abstract
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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.
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