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PDBsum entry 1vwt
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Oxygen transport
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PDB id
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1vwt
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Novel water-Mediated hydrogen bonds as the structural basis for the low oxygen affinity of the blood substitute candidate rhb(alpha 96val--≫trp).
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Authors
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Y.A.Puius,
M.Zou,
N.T.Ho,
C.Ho,
S.C.Almo.
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Ref.
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Biochemistry, 1998,
37,
9258-9265.
[DOI no: ]
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PubMed id
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Abstract
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One of the most promising approaches for the development of a synthetic blood
substitute has been the engineering of novel mutants of human hemoglobin (Hb) A
which maintain cooperativity, but possess lowered oxygen affinity. We describe
here two crystal structures of one such potential blood substitute, recombinant
(r) Hb(alpha 96Val-->Trp), refined to 1.9 A resolution in an alpha-aquomet,
beta-deoxy T-state, and to 2.5 A resolution in a carbonmonoxy R-state. On the
basis of molecular dynamics simulations, a particular conformation had been
predicted for the engineered Trp residue, and the lowered oxygen affinity had
been attributed to a stabilization of the deoxy T-state interface by alpha
96Trp-beta 99Asp hydrogen bonds. Difference Fourier maps of the T-state
structure clearly show that alpha 96Trp is in a conformation different from that
predicted by the simulation, with its indole side chain directed away from the
interface and into the central cavity. In this conformation, the indole nitrogen
makes novel water-mediated hydrogen bonds across the T-state interface with beta
101Glu. We propose that these water-mediated hydrogen bonds are the structural
basis for the lowered oxygen affinity of rHb(alpha 96Val-->Trp), and discuss
the implications of these findings for future molecular dynamics studies and the
design of Hb mutants.
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Secondary reference #1
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Title
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A novel low oxygen affinity recombinant hemoglobin (alpha96val--≫ trp): switching quaternary structure without changing the ligation state.
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Authors
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H.W.Kim,
T.J.Shen,
D.P.Sun,
N.T.Ho,
M.Madrid,
C.Ho.
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Ref.
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J Mol Biol, 1995,
248,
867-882.
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PubMed id
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Secondary reference #2
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Title
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Production of unmodified human adult hemoglobin in escherichia coli.
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Authors
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T.J.Shen,
N.T.Ho,
V.Simplaceanu,
M.Zou,
B.N.Green,
M.F.Tam,
C.Ho.
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Ref.
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Proc Natl Acad Sci U S A, 1993,
90,
8108-8112.
[DOI no: ]
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PubMed id
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