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PDBsum entry 1cik
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Oxygen storage/transport
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PDB id
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1cik
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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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Waterproofing the heme pocket. Role of proximal amino acid side chains in preventing hemin loss from myoglobin.
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Authors
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E.C.Liong,
Y.Dou,
E.E.Scott,
J.S.Olson,
G.N.Phillips.
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Ref.
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J Biol Chem, 2001,
276,
9093-9100.
[DOI no: ]
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PubMed id
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Abstract
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The ability of myoglobin to bind oxygen reversibly depends critically on
retention of the heme prosthetic group. Globin side chains at the Leu(89)(F4),
His(97)(FG3), Ile(99)(FG5), and Leu(104)(G5) positions on the proximal side of
the heme pocket strongly influence heme affinity. The roles of these amino acids
in preventing heme loss have been examined by determining high resolution
structures of 14 different mutants at these positions using x-ray
crystallography. Leu(89) and His(97) are important surface amino acids that
interact either sterically or electrostatically with the edges of the porphyrin
ring. Ile(99) and Leu(104) are located in the interior region of the proximal
pocket beneath ring C of the heme prosthetic group. The apolar amino acids
Leu(89), Ile(99), and Leu(104) "waterproof" the heme pocket by forming
a barrier to solvent penetration, minimizing the size of the proximal cavity,
and maintaining a hydrophobic environment. Substitutions with smaller or polar
side chains at these positions result in exposure of the heme to solvent, the
appearance of crystallographically defined water molecules in or near the
proximal pocket, and large increases in the rate of hemin loss. Thus, the
naturally occurring amino acid side chains at these positions serve to prevent
hydration of the His(93)-Fe(III) bond and are highly conserved in all known
myoglobins and hemoglobins.
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Figure 1.
Fig. 1. Space-filling representation of the proximal heme
pocket of sperm whale myoglobin showing the position of the
Leu89(F4) side chain (dark, space-filling) relative to the heme
(shown in stick representation).
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Figure 5.
Fig. 5. Stereo view of superposed stick representations
of the heme pocket of sperm whale myoglobin showing tilting of
the heme because of substitutions at position 99(FG5). Wild-type
protein (Ile^99) is shown in yellow, I99V is in blue, and I99A
is in red.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2001,
276,
9093-9100)
copyright 2001.
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