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PDBsum entry 1hec
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Lyase(oxo-acid)
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PDB id
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1hec
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References listed in PDB file
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Key reference
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Title
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Structural consequences of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase ii.
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Authors
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S.K.Nair,
D.W.Christianson.
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Ref.
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Biochemistry, 1993,
32,
4506-4514.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
84%.
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Abstract
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The three-dimensional structures of Leu-198-->Glu, Leu-198-->His,
Leu-198-->Arg, and Leu-198-->Ala variants of human carbonic anhydrase II
(CAII) have each been determined by X-ray crystallographic methods to a
resolution of 2.0 A. The side chain of Leu-198 is located at the mouth of the
active site hydrophobic pocket, and this pocket is required for substrate
association. Hydrophobic-->hydrophilic amino acid substitutions at the mouth
of the pocket decrease kcat/KM for CO2 hydration: the CO2 hydrase activities of
Leu-198-->Glu, Leu-198-->His, and Leu-198-->Arg CAIIs are diminished
19-fold, 10-fold, and 17-fold, respectively, relative to the wild-type enzyme;
however, the substitution of a compact aliphatic side chain for Leu-198 has a
smaller effect on catalysis, in that Leu-198-->Ala CAII exhibits only a
3-fold decrease in CO2 hydrase activity [Krebs, J. F., Rana, F., Dluhy, R. A.,
& Fierke, C. A. (1993) Biochemistry (preceding paper in this issue)]. It is
intriguing that CO2 hydrase activity is not severely diminished in
Leu-198-->Arg CAII, even though the side chain of Arg-198 blocks the
hydrophobic pocket. Therefore, the bulky side chain of Arg-198 must be
reasonably mobile in order to accommodate substrate association. Significantly,
a residue larger than the wild-type Leu-198 side chain does not necessarily
block the substrate association pocket; e.g., the side chain of Glu-198 packs
against a hydrophobic patch, the net result of which is a wider mouth for the
pocket.(ABSTRACT TRUNCATED AT 250 WORDS)
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